WO2025257633A1

WO2025257633A1 - Long-acting castor oil-containing injectable formulations and methods of use thereof

Info

Publication number: WO2025257633A1
Application number: PCT/IB2025/055045
Authority: WO
Inventors: Samuel David BELL; Peter M CHEIFETZ; Edson DeSouza MOURA; Carol Belansky; Siddhi M DUDHAT; Ronald DOMALAON
Original assignee: Boehringer Ingelheim Vetmedica GmbH
Current assignee: Boehringer Ingelheim Vetmedica GmbH
Priority date: 2024-06-12
Filing date: 2025-05-14
Publication date: 2025-12-18
Anticipated expiration: 2026-12-12

Abstract

Described herein are long-acting injectable formulations for the treatment or prevention of a parasitic infestation or infection in an animal. The formulation contains a parasiticidal isoxazoline active agent; and castor oil or a combination of castor oil and a second natural oil. The amount of castor oil in the formulation or the combination of castor oil and the second natural oil is at least 40% (w/w). The formulation can be in the form of a solution or a suspension, and physically stable at standard ambient temperature and pressure for at least 1 month. Typically, the formulation is at least 80% effective at treating or preventing infestation by fleas and/or ticks for at least 6 months following a single administration to the animal.

Description

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 1 - LONG-ACTING CASTOR OIL-CONTAINING INJECTABLE FORMULATIONS AND METHODS OF USE THEREOF FIELD OF THE INVENTION 5 This invention is generally in the field of formulations of isoxazolines and methods of use thereof. CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63/658,897, filed June 12, 2024, which is incorporated herein by reference. 10 BACKGROUND OF THE INVENTION Animals, such as mammals and birds, are often susceptible to parasite infestations/infections. These parasites may be ectoparasites, such as fleas, ticks and parasitic flies, and endoparasites such as nematodes and other worms. Domesticated animals, such as 15 cats and dogs, are often infested with one or more of the following ectoparasites: fleas (e.g. Ctenocephalides spp., such as Ctenocephalides felis and the like); ticks (e.g. Rhipicephalus spp., Ixodes spp., Dermacentor spp., Amblyomma spp., and the like); mites (e.g. Demodex spp., Sarcoptes spp., Otodectes spp., and the like); lice (e.g. Trichodectes spp., Cheyletiella spp., Linognathus spp., Bovicola ovis, Bovicola bovis, and the like); mosquitoes (Aedes spp., 20 Culex spp., Anopheles spp. and the like); and flies (Haematobia spp., Musca spp., Stomoxys spp., Dermatobia spp., Cochliomyia spp. and the like). Fleas are a particular problem because not only do they adversely affect the health of the animal or human, but they also cause a great deal of psychological stress. Moreover, fleas can transmit pathogenic agents to animals and humans, such as tapeworm (Dipylidium 25 caninum). Ticks are also harmful to the physical and psychological health of the animal or human. However, the most serious problem associated with ticks is that they are vectors of pathogenic agents in both humans and animals. Major diseases which may be transmitted by ticks include borreliosis (Lyme disease caused by Borrelia burgdorferi), babesiosis (or piroplasmosis caused by Babesia spp.) and rickettsioses (e.g., Rocky Mountain spotted fever). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 2 - Ticks also release toxins which cause inflammation or paralysis in the host. Occasionally, these toxins are fatal to the host. Farm animals are also susceptible to parasite infestations. For example, cattle and other bovines are affected by a large number of parasites. A parasite that is prevalent among cattle 5 in some regions are ticks of the genus Rhipicephalus, especially those of the species microplus (cattle tick), decoloratus and annulatus. Ticks such as Rhipicephalus microplus (formerly Boophilus microplus) are difficult to control because they lay eggs in the pasture where farm animals graze. This species of ticks is considered a one-host tick and spends immature and adult stages on one animal before the female engorges and falls off the host to lay eggs in the 10 environment. The life cycle of the tick is approximately three to four weeks. In addition to cattle, Rhipicephalus microplus may also infest buffalo, horses, donkeys, goats, sheep, deer, pigs, and dogs. A heavy tick burden on animals can decrease production and damage hides as well as transmit diseases such as babesiosis (“cattle fever”) and anaplasmosis. Animals and humans also suffer from endoparasitic infections including, for example, 15 helminthiasis which is caused by parasitic worms categorized as cestodes (tapeworm), nematodes (roundworm) and trematodes (flatworm or flukes). These parasites adversely affect the nutrition of the animal and cause severe economic losses in pigs, sheep, horses, and cattle as well as affecting companion animals and poultry. Other parasites, which occur in the gastrointestinal tract of animals and humans, include those from the genus Ancylostoma, 20 Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Toxocara, Toxascaris, Trichuris, Enterobius, and parasites that are found in the blood or other tissues and organs, such as filarial worms and the extra intestinal stages of Strongyloides, Toxocara and Trichinella. Isoxazole and isoxazoline-containing compounds have been demonstrated to be effective against parasites that harm animals. For example, US 7,964,204 (to DuPont) 25 discloses isoxazoline compounds that are active against ectoparasites and/or endoparasites. US 2010/0254960 A1, WO 2007/070606 A2, WO 2007/123855 A2, WO 2010/003923 A1, US 7951828, US 7662972, US 2010/0137372 A1, US 2010/0179194 A2, US 2011/0086886 A2, US 2011/0059988 A1, US 2010/0179195 A1, WO 2007/075459 A2, and US 7951828 and US 7,662,972 disclose various other parasiticidal isoxazoline compounds. Other publications that 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 3 - disclose various other parasiticidal isoxazoline compounds and compositions thereof include WO 2007/079162 A1, WO 2008/154528 A1, WO 2009/002809 A2, WO 2011/149749 A1, WO 2014/439475 A1, US 8466115, WO 2012/120399, WO 2014/039484, WO 2014/189837, WO 2012/120135 A1, and US 9609869. WO 2012/089623 discloses topical localized 5 isoxazoline compositions containing glycofurol. WO 2013/039948 A1 discloses topical veterinary compositions containing at least one isoxazoline active agent. WO 2013/119442 A1 discloses oral veterinary compositions, such as a soft chew containing at least one isoxazoline active agent. In addition to topical and oral dosage forms, it is also possible to formulate active 10 agents as long-acting compositions, depending upon, for example, the physiochemical properties of the individual active agent, such as solubility, bioavailability, etc. However, these compositions suffer from one or more of the following drawbacks: irritation at injection sites, low physical stability (which requires reconstitution before injection), unfavorable plasma active agent concentrations at extended time (e.g., 15 approximately 3 months) following administration, and complex manufacturing processes (which may lead to plenty of failure modes during scaling up processes). For example, the compositions as disclosed in WO 2019/091936 require mixing two or more components and/or reconstitution to form the formulation before administration, which involves more steps with more chance of spilling, administering the wrong dose, and/or contamination, etc. 20 There remains a need for injectable isoxazoline formulations with improved properties, such as improved physical stability, favorable plasma isoxazoline concentrations at extended time following injection, prolonged efficacy against parasites (e.g., fleas and ticks), and/or ease of preparation. There is also a need for injectable isoxazoline formulations with low or reduced irritation at the injection site compared to existing injectable isoxazoline formulations. 25 Therefore, it is the object of the present invention to provide injectable isoxazoline formulations with one or more improved properties. It is another object of the present invention to provide methods for using the injectable isoxazoline formulations for treating or preventing parasitic infestations or infections in animals. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 4 - SUMMARY OF THE INVENTION Long-acting injectable formulations for the treatment or prevention of a parasitic infestation or infection in an animal are described. The formulation contains a parasiticidal 5 isoxazoline active agent; and a carrier that contains castor oil or a combination of castor oil and a second natural oil. The amount of castor oil in the formulation or the combination of castor oil and the second natural oil is at least 40% (w/w). The formulation can be in the form of a solution. In these forms, the carrier further contains one or more solubilizers and/or one or more emulsifiers, where the parasiticidal 10 isoxazoline active agent is dissolved in the carrier. Alternatively, the formulation can be in the form of a suspension, where the parasiticidal isoxazoline active agent is in the form of particles, and the particles are suspended in the carrier. The formulation can be physically stable at standard ambient temperature and pressure for at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year. 15 Typically, the formulation is at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing infestation by fleas and/or ticks for at least 6 months following a single administration to the animal. The parasiticidal isoxazoline active agent in the formulation can be any suitable isoxazoline compound. An example of the parasiticidal isoxazoline active agent in the 20 formulation can have a structure of: O F₃ . For examp , ulation has a structure of: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 5 - F3 . Optionally, the carrier further contains one or more pharmaceutically acceptable excipients, such as a viscosity modifier (ethyl oleate, ethanol, etc.), an emulsifier (Capryol®, 5 Labrasol®, polysorbate, etc.), a solubilizer (such as glycerol formal, glycofurol, glycerol, propylene carbonate, etc.), an antioxidant (such as butylated hydroxy anisole (BHA)), or a preservative, or a combination thereof. When the carrier contains a natural oil mixture of castor oil and a second natural oil, the second natural oil can be cottonseed oil, linseed oil, corn (maize) oil, coconut oil, palm 10 kernel oil, babassu oil, olive oil, peanut oil, arachis oil, sesame oil, soybean oil, safflower oil, perilla oil, oiticica oil, sunflower oil, gourd oil, grape seed oil, sesame oil, hazelnut oil, apricot oil, macadamia oil, avocado oil, jojoba oil, karite butter, liquid triglycerides of fatty acids comprising from 4 to 24 carbon atoms (such as medium chain-triglycerides (MCT), e.g., glycerol triesters of caprylic and capric acid, Miglyol^®810, Miglyol^®812, etc. ), purcellin oil,15 isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, 2- octyldodecyl erucate, isostearyl isostearate, a triglyceride of fractionated plant fatty acids with chain lengths of C₈ and C₁₀ combined with linoleic acid, (i.e., caprylic/capric/linoleic triglyceride, e.g., Miglyol^® 818, supplied by IOI Oleo), a glycerin ester of fractionated plant fatty acids with chain lengths of C8 and C10 combined with succinic acid (i.e., 20 caprylic/capric/succinic triglyceride, e.g., Miglyol^® 829 ECO or Miglyol^®829, supplied by ICI Oleo), propylene glycol diester of saturated plant fatty acids with chain lengths of C8 and C10, e.g. Miglyol^® 840, propylene glycol esters of saturated plant fatty acids with chain lengths of C₈ and C₁₀, e.g., Labrafac^TM PG, propylene glycol dicaprylate/dicaprate NF (supplied by Gattefosse), propylene glycol esters of any one or more of succinic acid, oleic acid, linoleic 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 6 - acid, and alpha-linolenic acid, fish oil, krill oil, omega 3 oil, omega 6 oil, or a mixture thereof. For example, the formulation contains a mixture of castor oil and cottonseed oil, or a mixture of castor oil and a glycerol triester of caprylic and capric acid. The formulations disclosed herein can be injected into an animal for treating or 5 preventing parasites in the animal. Typically, the formulation is at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing infestation by fleas and or ticks for at least 6 months following a single administration to the animal. Optionally, in the single administration, the formulation can be injected at one site or more than one site of the animal, such as in the left and right shoulders of the animal. 10 DETAILED DESCRIPTION OF THE INVENTION I. Injectable Formulations Injectable long-acting formulations (also referred to herein as “formulations,” “injectable formulations,” “long-acting injectable” or “long-acting formulations”) containing 15 (i) a parasiticidal isoxazoline active agent (also referred to herein as “isoxazoline active agent,” “isoxazoline compound,” or “isoxazoline”) and (ii) a carrier, where the carrier contains castor oil or a mixture of castor oil and one or more other natural oil(s) for the treatment or prevention of a parasitic infestation or infection in animals are disclosed herein. Typically, the amount of castor oil in the formulation or the mixture of castor oil and the other 20 natural oil(s) in the formulation is at least 40% (w/w). Thus, in one aspect the invention according to the present disclosure provides a long- acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal, especially a non-human animal, comprising: i. at least one parasiticidal isoxazoline active agent; and 25 ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 7 - According to one embodiment, the non-human animal is a cat and/or a dog, especially a dog. In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation 5 or infection in a dog comprising: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and 10 the second natural oil in the formulation is at least 40% (w/w). In yet another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for the treatment and/or prevention of a flea and/or a tick infestation in a dog comprising: i. at least one parasiticidal isoxazoline active agent; and 15 ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 20 The formulations of the invention according to the present disclosure may contain one or more pharmaceutically acceptable excipients, such as viscosity modifiers (ethyl oleate, ethanol, etc.), emulsifiers (Capryol, Labrasol, polysorbate, etc.), solubilizers (such as glycerol formal, glycofurol, glycerol, propylene carbonate, etc.), etc. 25 In some embodiments, the invention according to the present disclosure provides a long-acting injectable isoxazoline formulation which does not rely upon a polymer for providing at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%,at least 98%, and/or at least 99% efficacy against ectoparasites, including but not limited to ticks and/or fleas, for at least 3 months, at least 4 months, at least 5 months, at least 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 8 - 6 months, at least 7 months, at least 8 months, at least 9 months, more than 6 months, and more than 9 months. The term “long-acting”, as used herein refers to embodiments of the isoxazoline injectable formulations of the invention according to the present disclosure that provide at 5 least 75% efficacy against parasites, especially, ticks and/or fleas, for a duration of at least 3 months, preferably a duration of at least 4 months, more preferably a duration of at least 5 months, and most preferably a duration of at least 6 months. In one embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 80% efficacy against ticks and/or fleas for a duration 10 of at least 3 months, at least 4 months, at least 5 months, and especially at least 6 months. In one embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 85% efficacy against ticks and/or fleas for a duration of at least 3 months, at least 4 months, at least 5 months, and especially at least 6 months. In one embodiment, the long-acting injectable formulations of the invention according 15 to the present disclosure provide at least 90% efficacy against ticks and/or fleas for a duration of at least 3 months, at least 4 months, at least 5 months, and especially at least 6 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 80% efficacy against ticks and/or fleas for a duration of at least 3 months. 20 In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 80% efficacy against ticks and/or fleas for a duration of at least 4 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 80% efficacy against ticks and/or fleas for 25 a duration of at least 5 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 80% efficacy against ticks and/or fleas for a duration of at least 6 months. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 9 - In yet another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 85% efficacy against ticks and/or fleas for a duration of at least 3 months. In another embodiment, the long-acting injectable formulations of the invention 5 according to the present disclosure provide at least 85% efficacy against ticks and/or fleas for a duration of at least 4 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 85% efficacy against ticks and/or fleas for a duration of at least 5 months. 10 In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 85% efficacy against ticks and/or fleas for a duration of at least 6 months. In still another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 90% efficacy against ticks and/or fleas for 15 a duration of at least 3 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 90% efficacy against ticks and/or fleas for a duration of at least 4 months. In another embodiment, the long-acting injectable formulations of the invention 20 according to the present disclosure provide at least 90% efficacy against ticks and/or fleas for a duration of at least 5 months. In yet another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 90% efficacy against ticks and/or fleas for a duration of at least 6 months. 25 In one embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 95% efficacy against ticks and/or fleas for a duration of at least 3 months. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 10 - In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 95% efficacy against ticks and/or fleas for a duration of at least 4 months. In another embodiment, the long-acting injectable formulations of the invention 5 according to the present disclosure provide at least 95% efficacy against ticks and/or fleas for a duration of at least 5 months. In another embodiment, the long-acting injectable formulations of the invention according to the present disclosure provide at least 95% efficacy against ticks and/or fleas for a duration of at least 6 months. 10 In one embodiment, the invention according to the present disclosure provides a long- acting injectable formulation that does not contain a poly(lactide-co-glycolide) copolymer ("PLGA") such as the PLGA that is contained in the isoxazoline formulations disclosed in WO2016164487A1. In another embodiment, the invention according to the present disclosure provides a 15 long-acting injectable isoxazoline formulation that does not contain a liquid polyethylene glycol (“PEG”) that is liquid at room temperature such as the liquid PEGs and isoxazoline formulations as disclosed in WO2017147352A and WO2016138339A1. In yet another embodiment, the invention according to the present disclosure provides a long-acting injectable isoxazoline formulation that does not contain a poloxamer including 20 but not limited to the poloxamers in the isoxazoline formulations as disclosed in WO2016138339A1. In a preferred embodiment, the invention according to the present disclosure does not comprise liquid poloxamers that are liquid at 20-25°C. In one embodiment, the invention according to the present disclosure provides a long-acting injectable isoxazoline formulation that does not contain poloxamer 124 or poloxamer 181. 25 According to one embodiment, the invention according to the present disclosure provides a long-acting injectable isoxazoline formulation does not contain any two or more polymers selected from the group consisting of PEG, poloxamer, and PLGA. The formulations disclosed herein can be in a solution form or a suspension form for injection (e.g., intramuscular administration, intravenous administration, intraperitoneal 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 11 - administration, and subcutaneous administration), in particular subcutaneous injection, to an animal subject, including, but not limited to, a non-human animal subject such as a dog and/or a cat. The formulations disclosed herein generally demonstrate one or more of the following 5 properties: high physical stability (e.g., no clumping in the formulation for at least 1 month by visual inspection), low irritation at the injection site (e.g., an ISR score ≤ 2 for dogs), favorable plasma isoxazoline concentration at extended time following injection (e.g., a plasma isoxazoline concentration ≥ 30 ng/mL in dogs at 180 days following injection), and prolonged efficacy against parasites (e.g., at least 75% effective against ticks and/or at least 10 75% effective against fleas for at least 4 months, at least 5 months or at least 6 months). For example, the formulations of the invention according to the present disclosure have good physical stability (e.g., no clumping in the formulation for at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year by visual inspection), low irritation at the injection site (e.g., an ISR score ≤ 2 for dogs), and high efficacy (e.g., at least 15 70%) against a broad spectrum of ectoparasites and/or endoparasites, especially fleas and/or ticks, for a prolonged period of time, e.g., a period from four months to 1 year, of at least 4 months, of at least 6 months, or of more than 6 months. The formulations according to the invention of the present disclosure can be provided as a ready-to-use formulation or provided in a kit. For example, the kit may include a first 20 container of at least one parasiticidal isoxazoline active agent and a second container of carrier, which is a pharmaceutically acceptable excipient for forming a solution or suspension of the parasiticidal isoxazoline active agent. One or more containers may be vials to facilitate reconstitution immediately before administration. In some embodiments, the invention according to the present disclosure provides 25 formulations in solution form or suspension form that are physically stable (e.g., no clumping in the formulation for at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year by visual inspection) at standard ambient temperature and pressure and are provided as ready-to-use formulations that do not involve reconstitution or combining two or more components to form the formulation to be administered. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 12 - In one aspect, the invention according to the present disclosure provides a kit for treating or preventing a parasite infestation in an animal, comprising a) an isoxazoline active agent according to any one of formulae I-VI, or a pharmaceutically acceptable salt thereof; 5 b) a vehicle comprising a pharmaceutically acceptable excipient capable of forming a suspension or solution with the compound of a); and c) instructions for combining the isoxazoline compound with the vehicle prior to injection. In one embodiment, the invention according to the present disclosure provides a kit for10 forming a suspension with the isoxazoline active agent according to any one of formulae I- VI, or a pharmaceutically acceptable salt thereof. In another embodiment, the invention according to the present disclosure provides a kit for forming a solution of the isoxazoline active agent according to any one of formulae I-VI, or a pharmaceutically acceptable salt thereof. 15 A. Active Agents 1. Parasiticidal Isoxazoline Active Agents The formulations disclosed herein contain a parasiticidal isoxazoline active agent, optionally more than one parasiticidal isoxazoline active agent. The isoxazoline active agent contained in the formulations can be any suitable isoxazoline compound, such as those 20 described in WO 2007/079162, WO 2007/075459 and US 2009/0133319, WO 2007/070606 and US 2009/0143410, WO 2009/003075, WO 2009/002809, WO 2009/024541, WO 2005/085216 and US 2007/0066617, WO 2008/122375, and/or WO2017147352. In some embodiments, the parasiticidal isoxazoline active agent or at least one of the parasiticidal isoxazoline active agents (when more than one parasiticidal isoxazoline active 25 agent are present) in the formulation has the structure of Formula (I), (II), (III), (IV), (V), or (VI) below, or a pharmaceutical acceptable salt thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 13 - wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and 5 B³ are independently selected from the group consisting of CR² and N; W is O or S; R¹ is C1- C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁶; each R² is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 10 haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, C₂-C₄ alkoxycarbonyl, —CN or —NO₂; each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, —CN or 15 —NO2; R⁴ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen 20 to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and C1-C2 alkoxy; each R⁶ is independently halogen, C1-C6 alkyl, C₁-C₆ alkoxy, C₁-C₆ alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, —CN or —NO₂; each25 R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1- 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 14 - C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C₂-C₇ alkylcarbonyl, C₂-C₇ alkoxycarbonyl, C₂-C₇ alkylaminocarbonyl, C₃- C9 dialkylaminocarbonyl, C2-C7 haloalkylcarbonyl, C2-C7 haloalkoxycarbonyl, C2-C7 haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; 5 or Q²; each R⁸ is independently halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁- C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — NO₂; each R⁹ is independently halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ 10 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, —CN, —NO2, phenyl or pyridinyl; R¹⁰ is H; or C1-C6 alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one of more halogen; R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl,15 C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R¹² is H; Q³; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂- C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S 20 and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and C1-C2 alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently 25 selected from R⁸; each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 15 - R₁ A₁ N Y wherein: R₁ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted 5 with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO2; X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, 10 alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; A₁ is oxygen; and A₂ is oxygen, NR₂ or CR₇R₈; G is G-1 or G-2; B₂ 15 B1, B2, B3, B4 and B5 are , halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, 20 alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 16 - R7C(O)NR8-, -CN or -NO2; or Y is Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13; R₂ R₁₂ R₁₃ R₂ N^R ₂ ^R ₃ OR₂ R R_{2 N 12} R₁₃ NR R N 4 , 4 alkyl, 5 alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R₁₀S(O)-, R₁₀S(O)₂-, R10C(O)-, R10C(S)-, R10R11NC(O)-, R10R11NC(S)- R10OC(O)-; R4, R5 and R6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R₇ and R₈ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, 10 alkenyl, haloalkenyl, alkynyl or haloalkynyl; R9 is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, 15 R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; R₁₀, R₁₁, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or R10 together with 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 17 - R11 form =O, =S or =NR2; or R12 together with R13 form =O, =S or =NR2; W is O, S or NR2; n is 1-4; and m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F₃C H CF N ₃ 5 or a pharmaceutically acceptable salt thereof; or o u a or a pharmaceutically acceptable salt thereof; or F₃C 1 O -T 10 wherein R¹, R² an , , Y is the diradical group S yl group which is unsubstituted or substituted by 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 18 - halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1- C₆-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y B 3b 5 wherein: Y is hydrogen, fluoro, chloro or bromo; R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or 10 fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof. In some embodiments, the formulations disclosed herein contain at least two parasiticidal isoxazoline active agents, where two or more of the isoxazolines has the structure of Formula (I), (II), (III), (IV), (V), or (VI), or a pharmaceutical acceptable salt thereof. In 15 other embodiments, the formulations disclosed herein contain two or more parasiticidal isoxazoline active agents, where each of the isoxazolines has the structure of Formula (I), (II), (III), (IV), (V), or (VI), or a pharmaceutical acceptable salt thereof. In some embodiments, the formulations according to the invention as disclosed herein contain the parasiticidal isoxazoline active agent of Formula (I). In some embodiments, the 20 formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (II). In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (III). In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (IV). In some forms, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 19 - (V). In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (VI). In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of (S)-Ia or (R)-Ia. O ^N O F₃ 5 F₃ In som parasiticidal 10 isoxazoline active agent of Formula (Ib): R5 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 20 - or a pharmaceutically acceptable salt thereof, wherein: R² is independently halogen, C1-C6 alkyl or C₁-C₆ haloalkyl; R⁴ is H or C₁-C₆ alkyl; R⁵ is C₁-C₄ alkyl optionally substituted with one or more R⁷; and R⁷ is C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylaminocarbonyl, C3-C9 dialkylaminocarbonyl, C2-C7 haloalkylcarbonyl, C2-C7 5 haloalkoxycarbonyl, C₂-C₇ haloalkylaminocarbonyl, C₃-C₉ dihaloalkylaminocarbonyl (e.g., - CH2C(O)NHCH2CF3); and n is 0, 12, or 3. In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (Ic): O CF O H ₃ 10 or a pharma independently H, halogen, C1-C3 alkyl or C1-C3 haloalkyl. In some embodiments, X¹ and X³ are independently halogen and X² is hydrogen. In some embodiments, X¹, X² and X³ are each independently halogen. In some embodiments, X¹ and X³ are each independently halogen and 15 X² is C₁-C₃ haloalkyl. In some embodiments, X¹ and X² are independently halogen and X³ is C1-C3 haloalkyl. In some embodiments, X¹ and X² are independently halogen and X³ is CF3. In some embodiments, X¹ and X³ are chloro and X² is hydrogen. In some embodiments, X¹, X² and X³ are each independently chloro or fluoro. In some embodiments, X¹ is chloro, X² is fluoro and X³ is CF3. In some embodiments, X¹ and X³ are chloro and X² is fluoro. In some 20 embodiments, X¹, X² and X³ are each chloro. In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (VIII): 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 21 - or a pharmaceutically ac o, chloro, iodo or fluoro; and X² is chloro, fluoro or CF₃; Y is Y-1, Y-2, Y-3, Y-4 where Z is N or CH, Y-5, or Y-6: 5 10 and Q is - , , , -C(O)NHCH2CH2SCH3 or (-CH2-)(-CH2-)N(CO)CH2S(O)2CH3. In some embodiments, X¹, X² and X³ is any one of the forms described above for Formula (Ic). In some embodiments, Y is Y-1. In some embodiments, Y is Y-2. In some 15 embodiments, Y is Y-3. In some embodiments, Y is Y-4. In some embodiments, Y is Y-5. In 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 22 - some embodiments, Y is Y-6. In some embodiments, Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-6, X¹ is fluoro, X² is chloro and Q is OH. In some embodiments, Y is Y-6, X¹ is fluoro, X² is fluoro and Q is OH. In some embodiments, Y is Y-6, X¹ is fluoro, X² is CF3 and Q is OH. In some embodiments, Y is Y-6, X¹ is chloro, X² is chloro and Q is 5 OH. In some embodiments, Y is Y-6, X¹ is chloro, X² is fluoro and Q is OH. In some embodiments, Y is Y-6, X¹ is chloro, X² is CF3 and Q is OH. In some embodiments, Y is Y-6, X¹ is bromo, X² is chloro and Q is OH. In some embodiments, Y is Y-6, X¹ is bromo, X² is fluoro and Q is OH. In some embodiments, Y is Y-6, X¹ is bromo, X² is CF₃ and Q is OH. In some embodiments, Y is Y-6, X¹ is iodo, X² is chloro and Q is OH. In some embodiments, Y 10 is Y-6, X¹ is iodo, X² is fluoro and Q is OH. In some embodiments, Y is Y-6, X¹ is iodo, X² is CF3 and Q is OH. In some embodiments, Y is Y-1, X¹ is fluoro, X² is CF3 and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-1, X¹ is chloro, X² is fluoro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-2, X¹ is fluoro, X² is chloro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-1, X¹ is chloro, 15 X² is chloro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-3, X¹ is fluoro, X² is chloro and Q is (-CH2-)(-CH2-)N(CO)CH2S(O)2CH3, where each terminal CH2 is bonded to the benzylic carbon of Y-3. In some embodiments, Y is Y-3, X¹ is fluoro, X² is CF₃ and Q is (-CH₂-)(-CH₂-)N(CO)CH₂S(O)₂CH₃, where each terminal CH₂ is bonded to the benzylic 20 carbon of Y-3. In some embodiments, Y is Y-4 where Z is CH, X¹ is fluoro, X² is chloro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-4 where Z is CH, X¹ is fluoro, X² is fluoro and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-4, X¹ is fluoro, X² is CF3 and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y- 4, X¹ is chloro, X² is chloro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y 25 is Y-4, X¹ is chloro, X² is fluoro and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-4, X¹ is chloro, X² is CF3 and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-5, X¹ is fluoro, X² is chloro and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-5, X¹ is fluoro, X² is fluoro and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-5, X¹ is fluoro, X² is 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 23 - CF3 and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-5, X¹ is chloro, X² is chloro and Q is -C(O)NHCH₂C(O)NHCH₂CF₃. In some embodiments, Y is Y-5, X¹ is chloro, X² is fluoro and Q is -C(O)NHCH2C(O)NHCH2CF3. In some embodiments, Y is Y-5, X¹ is chloro, X² is CF3 and Q is -C(O)NHCH2C(O)NHCH2CF3. 5 In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (Ie). 10 icidal isoxazoline active agent of Formula (S)-Ie. In some embodiments, the formulations disclosed herein contain the parasiticidal 15 isoxazoline active agent of any one of Formula II-1.001 to II-1.025 and II-2.001-II-2.018. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 24 - 2 B Compounds II-1.001 to II-1.025 Compound No. (Z)_p B⁵ B⁴ B³ B² B¹ R¹⁵ R¹⁶ F₃ F₃ F3 F₃ F₃ F3 F₃ F₃ F₃ 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 25 - 2 B 18 Compound No. (Z)_p B⁵ B⁴ B³ B² B¹ R¹⁵ R¹⁶ F₃ F₃ F3 F₃ F₃ F₃ In some embodiments, the formulations disclosed herein contain the parasiticidal 5 isoxazoline active agent of Formula (Va): 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 26 - F₃ In s asiticidal isoxazoline active agent of Formula (VIa): N O OH ns for depicting stereochemistry. To indicate stereo configuration, bonds rising from the plane of the drawing and towards the viewer are denoted by solid wedges wherein the broad end of the wedge is 10 attached to the atom rising from the plane of the drawing towards the viewer. Bonds going below the plane of the drawing and away from the viewer are denoted by dashed wedges wherein the narrow end of the wedge is attached to the atom further away from the viewer. Constant width lines indicate bonds with a direction opposite or neutral relative to bonds shown with solid or dashed wedges; constant width lines also depict bonds in molecules or 15 parts of molecules in which no particular stereo configuration is intended to be specified. The isoxazoline compounds contained in the formulations may exist as one or more conformational isomers due to restricted rotation about the amide bond bonded to the aryl or heteroaryl ring (e.g., the amide bonded to the naphthyl group in formula (I)). Mixtures of 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 27 - conformational isomers may be contained in the formulations. In addition, the formulations may contain isoxazoline compounds that are enriched in one conformer relative to others. In some embodiments, the more biologically active enantiomer is believed to be in (S) configuration. For example, the more biologically active enantiomers of isoxazoline 5 compounds of Formulas (Ia), (Ib), (Ic), (Ie), (II) to (VIa), and (VIII) have the (S) configuration at the chiral carbon of the isoxazoline ring. In some embodiments, the isoxazoline compound contained in the formulations are enriched in an enantiomer that displays significant in vitro and in vivo activity (the eutomer) with a favorable toxicity profile relative to a formulation enriched with the other corresponding enantiomer that displays significantly less in vitro and 10 in vivo activity (the distomer). When enantiomerically enriched, one enantiomer can be present in greater amounts than the other, and the extent of enrichment may be defined by an expression of enantiomeric excess ("ee"), which is defined as (2x-l)·100 %, where x is the mole fraction of the dominant enantiomer in the mixture (e.g., an ee of 20 % corresponds to a 60:40 ratio of enantiomers). In some embodiments, the formulations contain isoxazoline 15 compounds having at least a 50 % enantiomeric excess. In some embodiments, the formulations contain isoxazoline compounds that have at least a 75 % enantiomeric excess, at least a 90 % enantiomeric excess, or at least a 94 % enantiomeric excess of the more active isomer. In some embodiments, the formulations contain enantiomerically pure of the more active isomer (the eutomer). When a mixture of isoxazoline compounds having (S) and (R) 20 configurations is contained in the formulation, the two isomers can have any suitable ratio, such as from 20:1 to 1:20. In some embodiments, the formulations disclosed herein contain the parasiticidal isoxazoline active agent of Formula (S)-Ia below. F₃ 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 28 - (S)-Ia In some embodiments, the formulations disclosed herein contain two or more parasiticidal isoxazoline active agents, where at least one of the parasiticidal isoxazoline active agents has the structure of Formula (S)-Ia. 5 In some embodiments, the formulations disclosed herein contain one or more of the following isoxazoline active agents: O ^N O Ia, Ia, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 29 - c), O CF H ₃ Ic, 5 CF₃ Ic, e), 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 30 - F₃ Cl F₃ Cl 5 Cl F 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 31 - Va, or a pharmaceutically acceptable salt thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 32 - In one embodiment, the invention according to the present disclosure provides a long- acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent wherein the at least one 5 parasiticidal active agent has a structure of (Ia) O ^N O 3 ; ination of castor oil and a second natural oil, 10 wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In one embodiment, the invention according to the present disclosure provides a long- acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: 15 i. at least one parasiticidal isoxazoline active agent wherein the at least one parasiticidal active agent has a structure of (S)-Ia: O F₃ a 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 33 - ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 5 In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal preferably comprising: i. at least one parasiticidal isoxazoline active agent, wherein the at least one parasiticidal active agent has a structure of (Ia) O ^N O ble ii. a carrier comprising castor oil, wherein the amount of castor oil in the formulation is at least 40% (w/w). 15 In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation in an animal comprising: i. at least one parasiticidal isoxazoline active agent,, wherein the parasiticidal isoxazoline active agent has a structure of (S)-Ia:

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 34 - r a pharmaceutically accepta and 5 ii. a carrier comprising castor oil, wherein the amount of castor oil in the formulation is at least 40% (w/w). In one embodiment, the invention according to the present disclosure provides a long- acting injectable formulation for the treatment and/or prevention of a parasitic infestation or 10 infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent wherein the at least one parasiticidal active agent has a structure of (Ia) O 3 ; 15 . p g stor oil and a second natural oil, wherein the amount of the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 35 - In one embodiment, the invention according to the present disclosure provides a long- acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent wherein the at least one 5 parasiticidal active agent has a structure of (S)-Ia: O ^N O F₃ castor oil and a second natural oil, wherein the amount of the combination of castor oil and the second natural oil in the 10 formulation is at least 40% (w/w). Definitions Terms used herein will have their customary meaning in the art unless specified otherwise. 15 As used herein, percentage by weight is abbreviated % w/w or wt %. Unless expressly indicated otherwise, “%” as listed herein to designate a concentration is a percentage by weight. As used herein, standard ambient temperature refers to temperatures ranging from about 15 °C to about 30°C and standard ambient pressure is 1 atmosphere (atm), namely the 20 average air pressure at sea level at 15°C which is equivalent to 760 mm Hg, adjusted for higher elevations above sea level. From a practical consideration, the embodiments of the invention according to the present disclosure are physically and chemically stable during storage and shipment without 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 36 - the need for controlled temperature and pressure, hence, the formulations are physically and chemically stable at standard ambient temperature and standard ambient pressure. Standard ambient temperature and standard ambient pressure as defined herein encompasses the International Council for Harmonisation of Technical Requirements for 5 Pharmaceuticals for Human Use (ICH) stability test conditions. According to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), stability of a formulation over a period of time such as at least 12 months, is verified at a controlled temperature of 25°C ± 2 °C at 60% RH whereby, the pressure varies in dependence upon the actual temperature and actual relative humidity of the testing chamber. 10 Accordingly, in certain embodiments, the formulations according to the invention of the present disclosure are physically and chemically stable at standard ambient temperature and standard ambient pressure for a given period of time. In certain other embodiments, the formulations according to the invention of the present disclosure are physically and chemically stable at 25°C ± 2 °C at 60% RH (relative humidity) ± 5% RH, for a given period 15 of time, including but not limited to at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year. The term “essentially pure” indicates that a compound or an enantiomer is at least about 90% pure, at least about 95%, at least about 98% pure, or higher. The term “alkyl” refers to saturated straight, branched, primary, secondary or tertiary 20 hydrocarbons, including those having 1 to 20 atoms. In some embodiments, alkyl groups will include C1-C12, C1-C10, C1-C8, C1-C6 or C1-C4 alkyl groups. Examples of C1-C10 alkyl include, but are not limited to, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2- methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2- dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-25 methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2- dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1- ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, heptyl, octyl, 2-ethylhexyl, nonyl and decyl and their isomers. C₁-C₄- 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 37 - alkyl means for example methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2- methylpropyl or 1,1-dimethylethyl. Cyclic alkyl groups or “cycloalkyl” include those with 3 to 10 carbon atoms having single or multiple condensed rings. In some embodiments, cycloalkyl groups include C4-C7 or 5 C₃-C₄ cyclic alkyl groups. Non-limiting examples of cycloalkyl groups include adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. The alkyl groups described herein can be unsubstituted or substituted with one or more moieties selected from the group consisting of alkyl, halo, haloalkyl, hydroxyl, carboxyl, acyl, acyloxy, amino, alkyl- or dialkylamino, amido, arylamino, alkoxy, aryloxy, nitro, cyano, 10 azido, thiol, imino, sulfonic acid, sulfate, sulfonyl, sulfanyl, sulfinyl, sulfamoyl, ester, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrazine, carbamate, phosphoric acid, phosphate, phosphonate, or any other viable functional group that does not inhibit the biological activity of the compounds of the invention, either unprotected, or protected as necessary, as known to those skilled in the art, 15 for example, as taught in Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Third Edition, 1999, hereby incorporated by reference. “Alkylcycloalkyl,” “cycloalkylalkyl,” “alkylamino,” or “dialkylamino” contain an alkyl group as defined above linked to the other functional group, where the group is linked to the compound through the last group listed, as understood by those of skill in the art. 20 The term “alkenyl” refers to both straight and branched carbon chains which have at least one carbon-carbon double bond. In some forms, alkenyl groups may include C2-C20 alkenyl groups. In other forms, alkenyl includes C₂-C₁₂, C₂-C₁₀, C₂-C₈, C₂-C₆ or C₂-C₄ alkenyl groups. In some forms of alkenyl, the number of double bonds is 1-3, in some forms of alkenyl, the number of double bonds is one or two. Other ranges of carbon-carbon double 25 bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. “C2-C10-alkenyl” groups may include more than one double bond in the chain. Examples include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-methyl- ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1- methyl-2-propenyl, 2-methyl-2-propenyl; 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1- 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 38 - methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2- butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1- propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1- 5 methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1- methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1- methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1- methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1- dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl,10 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3- butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3- dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1- ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1- 15 ethyl-2-methyl-2-propenyl. “Alkynyl” refers to both straight and branched carbon chains which have at least one carbon-carbon triple bond. In some forms of alkynyl, the number of triple bonds is 1-3; in some forms of alkynyl, the number of triple bonds is one or two. In some forms, alkynyl groups include from C₂-C₂₀ alkynyl groups. In some forms, alkynyl groups may include C₂- 20 C12, C2-C10, C2-C8, C2-C6 or C2-C4 alkynyl groups. Other ranges of carbon-carbon triple bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. For example, the term ”C₂-C₁₀-alkynyl” as used herein refers to a straight-chain or branched unsaturated hydrocarbon group having 2 to 10 carbon atoms and containing at least one triple bond, such as ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl, n-but-1-yn-1-yl, n-but-25 1-yn-3-yl, n-but-1-yn-4-yl, n-but-2-yn-1-yl, n-pent-1-yn-1-yl, n-pent-1-yn-3-yl, n-pent-1-yn-4- yl, n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl, n-pent-2-yn-5-yl, 3-methylbut-1-yn- 3-yl, 3-methylbut-1-yn-4-yl, n-hex-1-yn-1-yl, n-hex-1-yn-3-yl, n-hex-1-yn-4-yl, n-hex-1-yn-5- yl, n-hex-1-yn-6-yl, n-hex-2-yn-1-yl, n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2-yn-6-yl, n- hex-3-yn-1-yl, n-hex-3-yn-2-yl, 3-methylpent-1-yn-1-yl, 3-methylpent-1-yn-3-yl, 3- 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 39 - methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl, 4-methylpent-1-yn-1-yl, 4-methylpent-2-yn-4- yl or 4-methylpent-2-yn-5-yl and the like. The term “haloalkyl” refers to an alkyl group, as defined herein, which is substituted by one or more halogen atoms. For example C1-C4-haloalkyl includes, but is not limited to, 5 chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1- chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2- trichloroethyl, pentafluoroethyl and the like. 10 The term “haloalkenyl” refers to an alkenyl group, as defined herein, which is substituted by one or more halogen atoms. The term “haloalkynyl” refers to an alkynyl group, as defined herein, which is substituted by one or more halogen atoms. “Alkoxy” refers to alkyl-O-, wherein alkyl is as defined above. Similarly, the terms 15 “alkenyloxy,” “alkynyloxy,” “haloalkoxy,” “haloalkenyloxy,” “haloalkynyloxy,” “cycloalkoxy,” “cycloalkenyloxy,” “halocycloalkoxy,” and “halocycloalkenyloxy” refer to the groups alkenyl-O, alkynyl-O-, haloalkyl-O-, haloalkenyl-O-, haloalkynyl-O-, cycloalkyl-O-, cycloalkenyl-O-, halocycloalkyl-O-, and halocycloalkenyl-O-, respectively, wherein alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, halocycloalkyl, and 20 halocycloalkenyl are as defined above. Examples of C1-C6-alkoxy include, but are not limited to, methoxy, ethoxy, C2H5-CH2O-, (CH3)2CHO-, n-butoxy, C2H5-CH(CH3)O-, (CH3)2CH- CH₂O-_, (CH₃)₃CO-, n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1- dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethyl-propoxy, 1-ethylpropoxy, n-hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy,25 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3- dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2- trimethylpropoxy, 1-ethyl-1-methylpropoxy, 1-ethyl-2-methylpropoxy and the like. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 40 - The term “alkylthio” refers to alkyl-S-, wherein alkyl is as defined above. Similarly, the terms “haloalkylthio,” “cycloalkylthio,” and the like, refer to haloalkyl-S- and cycloalkyl- S- where haloalkyl and cycloalkyl are as defined above. The term “alkylsulfinyl” refers to alkyl-S(O)-, wherein alkyl is as defined above. 5 Similarly, the term “haloalkylsulfinyl” refers to haloalkyl-S(O)- where haloalkyl is as defined above. The term “alkylsulfonyl” refers to alkyl-S(O)2-, wherein alkyl is as defined above. Similarly, the term “haloalkylsulfonyl” refers to haloalkyl-S(O)2- where haloalkyl is as defined above. 10 The term “alkylamino” and “dialkylamino” refer to alkyl-NH- and (alkyl)2N- where alkyl is as defined above. Similarly, the terms “haloalkylamino” refers to haloalkyl-NH- where haloalkyl is as defined above. The terms “alkylcarbonyl,” “alkoxycarbonyl,” “alkylaminocarbonyl,” and “dialkylaminocarbonyl” refer to alkyl-C(O)-, alkoxy-C(O)-, alkylamino-C(O)- and 15 dialkylamino-C(O)- where alkyl, alkoxy, alkylamino and dialkylamino are as defined above. Similarly, the terms “haloalkylcarbonyl,” “haloalkoxycarbonyl,” “haloalkylaminocarbonyl,” and “dihaloalkylaminocarbonyl” refer to the groups haloalkyl-C(O)-, haloalkoxy-C(O)-, haloalkylamino-C(O)- and dihaloalkylamino-C(O)- where haloalkyl, haloalkoxy, haloalkylamino and dihaloalkylamino are as defined above. 20 “Aryl” refers to a monovalent aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring or multiple condensed rings. In some embodiments, aryl groups include C₆-C₁₀ aryl groups. Aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, tetrahydronaphtyl, phenylcyclopropyl and indanyl. Aryl groups may be unsubstituted or substituted by one or more moieties selected from halogen, cyano, nitro, hydroxy, mercapto, 25 amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, halocycloalkenyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, cycloalkoxy, cycloalkenyloxy, halocycloalkoxy, halocycloalkenyloxy, alkylthio, haloalkylthio, cycloalkylthio, halocycloalkylthio, alkylsulfinyl, alkenylsulfinyl, alkynyl-sulfinyl, haloalkylsulfinyl, haloalkenylsulfinyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 41 - haloalkynylsulfinyl, alkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, haloalkyl-sulfonyl, haloalkenylsulfonyl, haloalkynylsulfonyl, alkylamino, alkenylamino, alkynylamino, di(alkyl)amino, di(alkenyl)-amino, di(alkynyl)amino, or trialkylsilyl. The terms “aralkyl” or “arylalkyl” refers to an aryl group that is bonded to the parent 5 compound through a diradical alkylene bridge, (-CH2-)_n, where n is 1-12 and where “aryl” is as defined above. “Heteroaryl” refers to a monovalent aromatic group of from 1 to 15 carbon atoms, preferably from 1 to 10 carbon atoms, having one or more oxygen, nitrogen, and sulfur heteroatoms within the ring, preferably 1 to 4 heteroatoms, or 1 to 3 heteroatoms. The nitrogen 10 and sulfur heteroatoms may optionally be oxidized. Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple condensed rings provided that the point of attachment is through a heteroaryl ring atom. Preferred heteroaryls include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinnyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, 15 isothiazolyl, pyrazolyl benzofuranyl, and benzothiophenyl. Heteroaryl rings may be unsubstituted or substituted by one or more moieties as described for aryl above. “Heterocyclyl,” “heterocyclic” or “heterocyclo” refer to fully saturated or unsaturated, cyclic groups, for example, 3 to 7 membered monocyclic or 4 to 7 membered monocyclic; 7 to 11 membered bicyclic, or 10 to 15 membered tricyclic ring systems, which have one or more 20 oxygen, sulfur or nitrogen heteroatoms in ring, preferably 1 to 4 or 1 to 3 heteroatoms. The nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system and may be unsubstituted or substituted by one or more moieties as described for aryl groups above. 25 Exemplary monocyclic heterocyclic groups include, but are not limited to, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2- oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 42 - pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, triazinyl, and the like. Exemplary bicyclic heterocyclic groups include, but are not limited to, indolyl, 5 benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetra- hydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl]or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), 10 tetrahydroquinolinyl and the like. Exemplary tricyclic heterocyclic groups include carbazolyl, benzidolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl, and the like. Halogen means the atoms fluorine, chlorine, bromine and iodine. The designation of “halo” (e.g. as illustrated in the term haloalkyl) refers to all degrees of substitutions from a single 15 substitution to a perhalo substitution (e.g. as illustrated with methyl as chloromethyl (-CH₂Cl), dichloromethyl (-CHCl2), trichloromethyl (-CCl3)). The term “enriched” refers to when the weight:weight ratio is at least approximately 1.05 or higher in favor of the enantiomer that displays significant in vitro and in vivo activity (the eutomer). 20 As noted above, it will be appreciated by those of skill in the art that certain isoxazoline compounds in the formulations may exist and be isolated as optically active and racemic forms. Compounds having one or more chiral centers, including at a sulfur atom, may be present as single enantiomers or diastereomers or as mixtures of enantiomers and/or diastereomers. For example, it is well known in the art that sulfoxide compounds may be 25 optically active and may exist as single enantiomers or racemic mixtures. In addition, compounds within the compositions of the invention may include one or more chiral centers, which results in a theoretical number of optically active isomers. Where compounds within the compositions of the invention include n chiral centers, the compounds may comprise up to 2ⁿ optical isomers. The present invention encompasses compositions comprising the specific 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 43 - enantiomers or diastereomers of each compound as well as mixtures of different enantiomers and/or diastereomers of the compounds of the invention that possess the useful properties described herein. In addition, the invention encompasses compositions comprising one or more conformational isomers (e.g., rotamers) as well as mixtures of conformational isomers. 5 Conformational isomers of the isoxazoline compounds may be produced by a restriction of rotation about the amide bond bonded to the aryl or heteroaryl ring (e.g., the amide bonded to the naphthyl group in formula (I)). The optically active forms can be prepared by, for example, resolution of the racemic forms by selective crystallization techniques, by synthesis from optically active precursors, by chiral synthesis, by chromatographic separation using a 10 chiral stationary phase or by enzymatic resolution. The isoxazoline compounds in the formulations may exist as polymorphic forms, including amorphous forms, and crystalline forms. In some embodiments, the invention according to the present disclosure provides long- acting injectable compositions containing substantially pure crystalline isoxazoline compound 15 forms. In some embodiments, preferably, there is less than 5%, more preferably less than 2%, and even more preferably less than 1% of any other crystal form, or amorphous form, of the isoxazoline compound present. In addition, the isoxazoline compounds in the formulations may exist as hydrates or solvates, in which a certain stoichiometric amount of water or a solvent is associated with the 20 molecule in the crystalline form. The compositions of the invention may include hydrates and solvates of the active agents. In some embodiments, the compositions of the invention may include up to 15% (w/w), up to 20% (w/w), or up to 30% (w/w) of a particular solid form. In some embodiments, the isoxazoline compounds in the formulations of the present disclosure are in a crystalline form whereby a solvate is bound in the crystal lattice, referred to 25 as a “solvate,” a “solvate polymorph”, and “solvate crystalline”. In certain embodiments, the invention of the present disclosure provides long-acting injectable formulations contain esafoxolaner, i.e. (S)-afoxolaner in crystalline polymorphic forms I or II (“Form I” or “Form II"). Crystalline forms I and II of esafoxolaner can be obtained by a process such as that disclosed in international patent application no. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 44 - PCT/US2018/026328, published as WO 2018/187623 A1, which is incorporated herein by reference in its entirety. Form I esafoxolaner is the form with the lower melting polymorph with a melting onset of ~143°C, a peak melting temperature of ~146°C and a normalized heat of fusion value of -61.7 J/g respectively. Form II has a melting onset of ~146°C, a peak 5 melting temperature of ~149°C and a normalized heat of fusion value of -65J/g respectively. In some embodiments, the isoxazoline compounds in the formulations are acid or base salts, where applicable. The term "acid salt" refers to salts of the compounds with all pharmaceutically acceptable inorganic or organic acids. Inorganic acids include mineral acids such as hydrohalic acids such as hydrobromic acid and hydrochloric acid, sulfuric acid, 10 phosphoric acids and nitric acid. Organic acids include all pharmaceutically acceptable aliphatic, alicyclic and aromatic carboxylic acids, dicarboxylic acids, tricarboxylic acids and fatty acids. In one embodiment of the acids, the acids are straight chain or branched, saturated or unsaturated C1-C20 aliphatic carboxylic acids, which are optionally substituted by halogen or by hydroxyl groups, or C6-C12 aromatic carboxylic acids. Examples of such acids are15 carbonic acid, formic acid, acetic acid, propionic acid, isopropionic acid, valeric acid, α- hydroxy acids such as glycolic acid and lactic acid, chloroacetic acid, benzoic acid, methane sulfonic acid, and salicylic acid. Examples of dicarboxylic acids include oxalic acid, malic acid, succinic acid, tartaric acid, fumaric acid, and maleic acid. An example of a tricarboxylic acid is citric acid. Fatty acids include all pharmaceutically acceptable saturated or unsaturated 20 aliphatic or aromatic carboxylic acids having 4 to 24 carbon atoms. Examples include butyric acid, isobutyric acid, sec-butyric acid, lauric acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and phenylsteric acid. Other acids include gluconic acid, glycoheptonic acid and lactobionic acid. The term “base salt” refers to salts of the compounds with all pharmaceutically acceptable inorganic or organic bases, including hydroxides, 25 carbonates or bicarbonates of alkali metal or alkaline earth metals. Salts formed with such bases include, for example, the alkali metal and alkaline earth metal salts, including, but not limited to, as the lithium, sodium, potassium, magnesium or calcium salts. Salts formed with organic bases include the common hydrocarbon and heterocyclic amine salts, which include, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 45 - for example, ammonium salts (NH4⁺), alkyl- and dialkylammonium salts, and salts of cyclic amines such as the morpholine and piperidine salts. 2. Amount of Parasiticidal Isoxazoline Active Agents The disclosed formulations typically contain an effective amount of the isoxazoline 5 active agent(s). As used herein, the term “effective amount” means any amount of the isoxazoline active agent(s) that is sufficient to achieve the desired therapeutic and/or prophylactic effect in an animal subject to which it is administered, for example, to treat and/or prevent an infestation and/or infection by a parasite. Depending on the parasites to be prevented and/or treated, and/or the specific route of injection, such an effective amount of the 10 isoxazoline active agent(s) can be between 0.01 to 1000 mg per kilogram body weight of the subject per day, between 0.1 and 500 mg, such as between 1 and 250 mg, between 1 and 200 mg, between 1 and 150 mg, between 1 and 100 mg, between 1 and 50 mg, for example about 1, 5, 10, 15, 20, 50, 100, 150, 200 or 250 mg, per kilogram body weight of the subject per day, which can be administered as a single daily dose, divided over one or more daily doses. The 15 amount(s) of the isoxazoline active agent(s) administered, the route of injection, and the further treatment regimen can be determined by the treating clinician or testing technologies, depending on factors such as the age, gender, and general condition of the animal subject, the nature and severity of the disease/symptoms being prevented and/or treated. In some embodiments, the amount of the isoxazoline active agent or total amount of 20 the isoxazoline active agents (when more than one isoxazoline active agent are present) in the formulation can be in a range from about 0.1 wt% to about 40 wt%, from about 0.1 wt% to about 35 wt%, from about 0.1 wt% to about 30 wt%, from about 0.1 wt% to about 25 wt%, from about 0.1 wt% to about 20 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 10 wt%, from about 1 wt% to about 40 wt%, from about 1 wt% to about 35 25 wt%, from about 1 wt% to about 30 wt%, from about 1 wt% to about 25 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 10 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 25 wt%, or from about 5 wt% to about 20 wt%, such as about 15 wt% or about 17.5 wt%. The term “total amount of the isoxazoline 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 46 - active agents” in the formulation refers to the sum of the weight of isoxazoline active agents in the formulation relative to the weight of the formulation (i.e., w/w). In some embodiments, the formulation is provided in a unit dosage form, and optionally is suitably packaged, for example in a box, blister, vial, bottle, sachet, ampoule or 5 in any other suitable single-dose or multi-dose holder or container (which can be properly labeled); optionally with one or more leaflets containing product information and/or instructions for use. In some embodiments, a unit dosage container can contain between 1 and 10,000 mg, and optionally contain between 5 and 10,000 mg, between 100 and 10,000 mg, between 5 and 5000 mg, between 100 and 5000 mg, between 5 and 3500 mg, between 100 and 10 3500 mg, of the isoxazoline active agent(s), e.g., about 5, 50, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10,000 mg, such as per single-dose vial. In some embodiments, a multi-dosage container can contain between 1 and 10,000 mg, and optionally contain between 5 and 10,000 mg, between 100 and 10,000 mg, between 5 and 5000 mg, between 100 and 5000 mg, between 5 and 3500 mg, between 100 and 3500 mg, of the 15 isoxazoline active agent(s), e.g., about 5, 50, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10,000 mg, such as per multi-dose vial. 3. Additional Active Agents Optionally, the formulations disclosed herein contain one or more other veterinary active agents in addition to isoxazoline active agents, such as one or more acaricides, 20 anthelmintics, anti-parasitics (e.g., ectoparasiticidal agents, endoparasiticidal agents), insecticides, etc. Veterinary active agents that can be included in the formulations are known (see, e.g., Plumb’ Veterinary Drug Handbook, 5^th Edition, ed. Donald C. Plumb, Blackwell Publishing, (2005) or The Merck Veterinary Manual, 9^th Edition, (January 2005)). Exemplary veterinary active agents suitable for use in the formulations include, but are 25 not limited to, acarbose, acepromazine maleate, acetaminophen, acetazolamide, acetazolamide sodium, acetic acid, acetohydroxamic acid, acetylcysteine, acitretin, acyclovir, albendazole, albuterol sulfate, alfentanil, allopurinol, alprazolam, altrenogest, amantadine, amikacin sulfate, aminocaproic acid, aminopentamide hydrogen sulfate, aminophylline/theophylline, amiodarone, amitriptyline, amlodipine besylate, ammonium chloride, ammonium molybdate, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 47 - amoxicillin, clavulanate potassium, amphotericin B desoxycholate, amphotericin B lipid- based, ampicillin, amprolium, antacids (oral), antivenin, apomorphione, apramycin sulfate, ascorbic acid, asparaginase, aspiring, atenolol, atipamezole, atracurium besylate, atropine sulfate, aurnofin, aurothioglucose, azaperone, azathioprine, azithromycin, baclofen, 5 barbituates, benazepril, betamethasone, bethanechol chloride, bisacodyl, bismuth subsalicylate, bleomycin sulfate, boldenone undecylenate, bromides, bromocriptine mesylate, budenoside, buprenorphine, buspirone, busulfan, butorphanol tartrate, cabergoline, calcitonin salmon, calcitrol, calcium salts, captopril, carbenicillin indanyl sodium, carbimazole, carboplatin, carnitine, carprofen, carvedilol, cefadroxil, cefazolin sodium, cefixime, clorsulon, 10 cefoperazone sodium, cefotaxime sodium, cefotetan disodium, cefoxitin sodium, cefpodoxime proxetil, ceftazidime, ceftiofur sodium, ceftiofur, ceftiaxone sodium, cephalexin, cephalosporins, cephapirin, charcoal (activated), chlorambucil, chloramphenicol, chlordiazepoxide, chlordiazepoxide +/- clidinium bromide, chlorothiazide, chlorpheniramine maleate, chlorpromazine, chlorpropamide, chlortetracycline, chorionic gonadotropin (HCG), 15 chromium, cimetidine, ciprofloxacin, cisapride, cisplatin, citrate salts, clarithromycin, clemastine fumarate, clenbuterol, clindamycin, clofazimine, clomipramine, claonazepam, clonidine, cloprostenol sodium, clorazepate dipotassium, clorsulon, cloxacillin, codeine phosphate, colchicine, corticotropin (ACTH), cosyntropin, cyclophosphamide, cyclosporine, cyproheptadine, cytarabine, dacarbazine, dactinomycin/actinomycin D, dalteparin sodium, 20 danazol, dantrolene sodium, dapsone, decoquinate, deferoxamine mesylate, deracoxib, deslorelin acetate, desmopressin acetate, desoxycorticosterone pivalate, detomidine, dexamethasone, dexpanthenol, dexraazoxane, dextran, diazepam, diazoxide (oral), dichlorphenamide, diclofenac sodium, dicloxacillin, diethylcarbamazine citrate, diethylstilbestrol (DES), difloxacin, digoxin, dihydrotachysterol (DHT), diltiazem, 25 dimenhydrinate, dimercaprol/BAL, dimethyl sulfoxide, dinoprost tromethamine, diphenylhydramine, disopyramide phosphate, dobutamine, docusate/DSS, dolasetron mesylate, domperidone, dopamine, doramectin, doxapram, doxepin, doxorubicin, doxycycline, edetate calcium disodium.calcium EDTA, edrophonium chloride, enalapril/enalaprilat, enoxaparin sodium, enrofloxacin, ephedrine sulfate, epinephrine, epoetin/erythropoietin, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 48 - eprinomectin, epsiprantel, erythromycin, esmolol, estradiol cypionate, ethacrynic acid/ethacrynate sodium, ethanol (alcohol), etidronate sodium, etodolac, etomidate, euthanasia agents w/pentobarbital, famotidine, fatty acids (essential/omega), felbamate, fentanyl, ferrous sulfate, filgrastim, finasteride, fipronil, florfenicol, fluconazole, flucytosine, fludrocortisone 5 acetate, flumazenil, flumethasone, flunixin meglumine, fluorouracil (5-FU), fluoxetine, fluticasone propionate, fluvoxamine maleate, fomepizole (4-MP), furazolidone, furosemide, gabapentin, gemcitabine, gentamicin sulfate, glimepiride, glipizide, glucagon, glucocorticoid agents, glucosamine/chondroitin sulfate, glutamine, glyburide, glycerin (oral), glycopyrrolate, gonadorelin, grisseofulvin, guaifenesin, halothane, hemoglobin glutamer-200 10 (OXYGLOBIN®), heparin, hetastarch, hyaluronate sodium, hydrazaline, hydrochlorothiazide, hydrocodone bitartrate, hydrocortisone, hydromorphone, hydroxyurea, hydroxyzine, ifosfamide, imidacloprid, imidocarb dipropinate, impenem-cilastatin sodium, imipramine, inamrinone lactate, insulin, interferon alfa-2a (human recombinant), iodide (sodium/potassium), ipecac (syrup), ipodate sodium, iron dextran, isoflurane, isoproterenol, 15 isotretinoin, isoxsuprine, itraconazole, ivermectin, kaolin/pectin, ketamine, ketoconazole, ketoprofen, ketorolac tromethamine, lactulose, leuprolide, levamisole, levetiracetam, levothyroxine sodium, lidocaine, lincomycin, liothyronine sodium, lisinopril, lomustine (CCNU), lufenuron, lysine, magnesium, mannitol, marbofloxacin, mechlorethamine, meclizine, meclofenamic acid, medetomidine, medium chain triglycerides, 20 medroxyprogesterone acetate, megestrol acetate, melarsomine, melatonin, meloxican, melphalan, meperidine, mercaptopurine, meropenem, metformin, methadone, methazolamide, methenamine mandelate/hippurate, methimazole, methionine, methocarbamol, methohexital sodium, methotrexate, methoxyflurane, methylene blue, methylphenidate, methylprednisolone, metoclopramide, metoprolol, metronidaxole, mexiletine, mibolerlone, 25 midazolam milbemycin oxime, mineral oil, minocycline, misoprostol, mitotane, mitoxantrone, morphine sulfate, moxidectin, naloxone, mandrolone decanoate, naproxen, narcotic (opiate) agonist analgesics, neomycin sulfate, neostigmine, niacinamide, nitazoxanide, nitenpyram, nitrofurantoin, nitroglycerin, nitroprusside sodium, nizatidine, novobiocin sodium, nystatin, octreotide acetate, olsalazine sodium, omeprozole, ondansetron, opiate antidiarrheals, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 49 - orbifloxacin, oxacillin sodium, oxazepam, oxibutynin chloride, oxymorphone, oxytretracycline, oxytocin, pamidronate disodium, pancreplipase, pancuronium bromide, paromomycin sulfate, parozetine, pencillamine, general information penicillins, penicillin G, penicillin V potassium, pentazocine, pentobarbital sodium, pentosan polysulfate sodium, 5 pentoxifylline, pergolide mesylate, phenobarbital, phenoxybenzamine, pheylbutazone, phenylephrine, phenypropanolamine, phenytoin sodium, pheromones, parenteral phosphate, phytonadione/vitamin K-1, pimobendan, piperazine, pirlimycin, piroxicam, polysulfated glycosaminoglycan, ponazuril, potassium chloride, pralidoxime chloride, prazosin, prednisolone/prednisone, primidone, procainamide, procarbazine, prochlorperazine, 10 propantheline bromide, propionibacterium acnes injection, propofol, propranolol, protamine sulfate, pseudoephedrine, psyllium hydrophilic mucilloid, pyridostigmine bromide, pyrilamine maleate, pyrimethamine, quinacrine, quinidine, ranitidine, rifampin, s-adenosyl-methionine (SAMe), saline/hyperosmotic laxative, selamectin, selegiline /l-deprenyl, sertraline, sevelamer, sevoflurane, silymarin/milk thistle, sodium bicarbonate, sodium polystyrene 15 sulfonate, sodium stibogluconate, sodium sulfate, sodum thiosulfate, somatotropin, sotalol, spectinomycin, spironolactone, stanozolol, streptokinase, streptozocin, succimer, succinylcholine chloride, sucralfate, sufentanil citrate, sulfachlorpyridazine sodium, sulfadiazine/trimethroprim, sulfamethoxazole/trimethoprim, sulfadimentoxine, sulfadimethoxine/ormetoprim, sulfasalazine, taurine, tepoxaline, terbinafline, terbutaline 20 sulfate, testosterone, tetracycline, thiacetarsamide sodium, thiamine, thioguanine, thiopental sodium, thiotepa, thyrotropin, tiamulin, ticarcilin disodium, tiletamine /zolazepam, tilmocsin, tiopronin, tobramycin sulfate, tocainide, tolazoline, telfenamic acid, topiramate, tramadol, trimcinolone acetonide, trientine, trilostane, trimepraxine tartrate w/prednisolone, tripelennamine, tylosin, urdosiol, valproic acid, vanadium, vancomycin, vasopressin, 25 vecuronium bromide, verapamil, vinblastine sulfate, vincristine sulfate, vitamin E/selenium, warfarin sodium, xylazine, yohimbine, zafirlukast, zidovudine (AZT), zinc acetate/zinc sulfate, zonisamide and mixtures thereof. In some embodiments, the formulations contain arylpyrazole compounds, such as phenylpyrazoles, in addition to the isoxazoline compounds. Examples of such arylpyrazole 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 50 - compounds include, but are not limited to. those described in U.S. Patent Nos. 6,001,384; 6,010,710; 6,083,519; 6,096,329; 6,174,540; 6,685,954 and 6,998,131. In some embodiments, the formulations contain one or more macrocyclic lactones or lactams, which can act as an acaricide, anthelmintic agent and/or insecticide, in addition to the 5 isoxazoline active agent(s). Macrocyclic lactones suitable for use in the formulations can be either natural products or semi-synthetic derivatives thereof. Exemplary suitable for use in the formulations include, but are not limited to, avermectins such as abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin and ML- 1,694,554; milbemycins such as milbemectin, milbemycin D, milbemycin oxime, moxidectin 10 and nemadectin; and the 5-oxo and 5-oxime derivatives of said avermectins and milbemycins. Additional examples of avermectins, milbemycins, and latidectins and semisynthetic derivatives thereof are described in U.S. Patent No. 4,310,519, U.S. Patent No. 4,199,569, U.S. Patent Nos. 4,468,390, 5,824,653, EP 0007812 A1, U.K. Patent Specification 1390 336, EP 0002916, New Zealand Patent No. 237086, inter alia, U.S. Patent No. 3,950,360, 15 the references cited in “The Merck Index” 12^th ed., S. Budavari, Ed., Merck & Co., Inc. Whitehouse Station, New Jersey (1996), WHO Drug Information, vol. 17, no. 4, pp. 263- 286, (2003), U.S. Patent Nos. 5,077,308, 4,859,657, 4,963,582, 4,855,317, 4,871,719, 4,874,749, 4,427,663, 4,310,519, 4,199,569, 5,055,596, 4,973,711, 4,978,677, 4,920,148 and EP 0667 054. 20 Examples of combinations of arylpyrazole compounds with macrocyclic lactones that can be used in the formulations include but are not limited to those described in U.S. Patent Nos. 6,426,333; 6,482,425; 6,962,713 and 6,998,131. Macrocyclic lactone compounds are known and can easily be obtained commercially or through synthesis techniques known in the art. Avermectins, ivermectin, and abamectin suitable for use in the formulations are known, 25 see, for example, “Ivermectin and Abamectin”, 1989, by M.H. Fischer and H. Mrozik, William C. Campbell, published by Springer Verlag., or Albers-Schönberg et al. (1981), “Avermectins Structure Determination”, J. Am. Chem. Soc., 103, 4216-4221. Doramectin suitable for use in the formulations are known, see, for example, “Veterinary Parasitology”, vol. 49, No. 1, July 1993, 5-15. Milbemycins suitable for use in the formulations are also 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 51 - known, see, for example, inter alia, to Davies H.G. et al., 1986, “Avermectins and Milbemycins”, Nat. Prod. Rep., 3, 87-121, Mrozik H. et al., 1983, Synthesis of Milbemycins from Avermectins, Tetrahedron Lett., 24, 5333-5336, U.S. Patent No. 4,134,973 and EP 0677054. 5 In some embodiments, the formulations contain one or more acaricides and/or insecticides known as insect growth regulators (IGRs), in addition to the isoxazoline active agent(s). Exemplary acaricides suitable for use in the disclosed formulations include, but are not limited to, pyrethrins (which include cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II and mixtures thereof) and pyrethroids, permethrin, and carbamates including, 10 but are not limited to, benomyl, carbanolate, carbaryl, carbofuran, methiocarb, metolcarb, promacyl, propoxur, aldicarb, butocarboxim, oxamyl, thiocarboxime and thiofanox. Additional examples of insect growth regulators suitable for use in the disclosed formulations are described in, for example, U.S. Patent Nos. 3,748,356, 3,818,047, 4,225,598, 4,798,837, 4,751,225, EP 0179022 or U.K. 2140010 as well as U.S. Patent Nos. 6,096,329 and 15 6,685,954. In some embodiments, the IGR contained in the disclosed formulations is a compound that mimics juvenile hormone, such as azadirachtin, diofenolan, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxyfen, tetrahydroazadirachtin and 4-chloro-2(2- chloro-2-methyl-propyl)-5-(6-iodo-3-pyridylmethoxy)pyridazine-3(2H)-one. In some embodiments, the IGR contained in the disclosed formulations is a chitin synthesis inhibitor, 20 such as chlorofluazuron, cyromazine, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumoron, lufenuron, tebufenozide, teflubenzuron, triflumuron, novaluron, 1-(2,6- difluorobenzoyl)-3-(2-fluoro-4-(trifluoromethyl)phenylurea, 1-(2,6-difluoro-benzoyl)-3-(2- fluoro-4-(1,1,2,2-tetrafluoroethoxy)-phenylurea, and 1-(2,6-difluorobenzoyl)-3-(2-fluoro-4- trifluoromethyl)phenylurea. 25 In some embodiments, the formulations contain one or more antinematodal agents, in addition to the isoxazoline active agent(s). Examples of antinematodal agents suitable for use in the formulations include, but are not limited to, benzimidazoles, imidazothiazoles, tetrahydropyrimidines, and organophosphate class of compounds. Examples of benzimidazoles suitable for use in the formulations include, but are not limited to, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 52 - thiabendazole, cambendazole, parbendazole, oxibendazole, mebendazole, flubendazole, fenbendazole, oxfendazole, albendazole, cyclobendazole, febantel, thiophanate and its o,o- dimethyl analogue. In some embodiments, the formulations contain imidazothiazole compounds, such as 5 tetramisole, levamisole, and/or butamisole, in addition to the isoxazoline active agent(s). In some embodiments, the formulations contain tetrahydropyrimidine active agents, such as pyrantel, oxantel, and morantel. In some embodiments, the formulations contain organophosphate active agents, such as coumaphos, trichlorfon, haloxon, naftalofos and dichlorvos, heptenophos, mevinphos, monocrotophos, TEPP, and tetrachlorvinphos. 10 In some embodiments, the formulations contain antinematodal compounds, such as phenothiazine and piperazine as the neutral compound or in various salt forms, diethylcarbamazine, phenols, e.g., disophenol, arsenicals, e.g., arsenamide, ethanolamines, e.g., bephenium, thenium closylate, and methyluridine; cyanine dyes including pyrvinium chloride, pyrvinium pamoate and dithiazanine iodide; isothiocyanates including bitoscanate, 15 suramin sodium, phthalofyne, and various natural products including, but not limited to, hygromycin B, α-santonin and kainic acid, in addition to the isoxazoline active agent(s). In some embodiments, the formulations contain anti-trematodal agents, in addition to the isoxazoline active agent(s). Suitable anti-trematodal agents for use in the formulations include, but are not limited to, the miracils such as miracil D and mirasan; praziquantel, 20 clonazepam and its 3-methyl derivative, oltipraz, lucanthone, hycanthone, oxamniquine, amoscanate, niridazole, nitroxynil, various bisphenol compounds known in the art including hexachlorophene, bithionol, bithionol sulfoxide and menichlopholan; various salicylanilide compounds including tribromsalane, oxyclozanide, diloxanide, rafoxanide, brotianide, bromoxanide and closantel; triclabendazole, diamfenetide, clorsulon, hetolin and emetine. 25 In some embodiments, the formulations contain anticestodal compounds, such as arecoline in various salt forms, bunamidine, niclosamide, nitroscanate, paromomycin and paromomycin II, in addition to the isoxazoline active agent(s). In some embodiments, the formulations contain active agents that are effective against arthropod parasites, in addition to the isoxazoline active agent(s). Examples of such active 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 53 - agents include, but are not limited to, bromocyclen, chlordane, DDT, endosulfan, lindane, methoxychlor, toxaphene, bromophos, bromophos-ethyl, carbophenothion, chlorfenvinphos, chlorpyrifos, crotoxyphos, cythioate, diazinon, dichlorenthion, diemthoate, dioxathion, ethion, famphur, fenitrothion, fenthion, fospirate, iodofenphos, malathion, naled, phosalone, phosmet, 5 phoxim, propetamphos, ronnel, stirofos, allethrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, flucythrinate, permethrin, phenothrin, pyrethrins, resmethrin, benzyl benzoate, carbon disulfide, crotamiton, diflubenzuron, diphenylamine, disulfiram, isobornyl thiocyanato acetate, methoprene, monosulfiram, pirenonylbutoxide, rotenone, triphenyltin acetate, triphenyltin hydroxide, deet, dimethyl phthalate, and the compounds 1,5a,6,9,9a,9b-10 hexahydro-4a(4H)-dibenzofurancarboxaldehyde (MGK-11), 2-(2-ethylhexyl)-3a,4,7,7a- tetrahydro-4,7-methano-1H-isoindole-1,3(2H)dione (MGK-264), dipropyl-2,5- pyridinedicarboxylate (MGK-326) and 2-(octylthio)ethanol (MGK-874). In some embodiments, the formulations contain antiparasitic agents that are biologically active peptides or proteins, in addition to the isoxazoline active agent(s), such as 15 depsipeptides, which act at the neuromuscular junction by stimulating presynaptic receptors belonging to the secretin receptor family resulting in the paralysis and death of parasites, for example, emodepside (see Willson et al., Parasitology, Jan. 2003, 126(Pt 1):79-86) or PF1022A and derivatives thereof. In some embodiments, the formulations contain neonicotinoid class of pesticides, in 20 addition to the isoxazoline active agent(s). Neonicotinoids can bind and inhibit insect specific nicotinic acetylcholine receptors. In some embodiments, the neonicotinoid compound contained in the formulations is imidacloprid, such as that used in Advantage^®, Advantage^® II, K9 Advantix^®, and K9 Advantix^® II sold by Bayer Animal Health and the oral soft-chewable composition Advantus™ from Piedmont Animal Health. Additional examples of imidacloprid 25 suitable for use in the formulations are described, for example, in U.S. Patent No. 4,742,060 or in EP 0892060. In some embodiments, the neonicotinoid compound contained in the formulations is nitenpyram, another active agent of the neonicotinoid class of pesticides, such as that used in the oral product CAPSTAR™ Tablets sold by Novartis Animal Health. Nitenpyram can interfere with normal nerve transmission and lead to the death of the insect. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 54 - In some embodiments, the formulations contain nodulisporic acid and its derivatives (a class of known acaricidal, anthelmintic, anti-parasitic and insecticidal agents), in addition to the isoxazoline active agent(s). Examples of nodulisporic acid and derivatives thereof that are suitable for use in the formulations are described, for example, in U.S. Patent No. 5,399,582, 5 5,962,499, 6,221,894 and 6,399,786. In some embodiments, the formulations contain anthelmintic compounds of the amino acetonitrile class (AAD), such as monepantel (ZOLVIX), and the like, in addition to the isoxazoline active agent(s). Examples of these compounds are described, for example, in WO 2004/024704 and U.S. Patent No. 7,084,280; Sager et al., Veterinary Parasitology, 2009, 159, 10 49-54; and Kaminsky et al., Nature vol. 452, 13 March 2008, 176-181. In some embodiments, the formulations contain aryloazol-2-yl cyanoethylamino compounds in addition to the isoxazoline active agent(s). Examples of cyanoethylamino compounds suitable for use in the formulations are described in US Patent No. 8,088,801 to Soll et al., and thioamide derivatives thereof, such as those described in U.S. Patent No. 15 7,964,621. In some embodiments, the formulations contain a paraherquamide compound and/or derivative of a paraherquamide compound, in addition to the isoxazoline active agent(s). Examples of paraherquamide and derivatives thereof suitable for use in the formulations include, but are not limited to, derquantel (see Ostlind et al., Research in Veterinary Science, 20 1990, 48, 260-61; and Ostlind et al., Medical and Veterinary Entomology, 1997, 11, 407-408). Additional examples of paraherquamide derivatives are described, for example, in WO 91/09961, WO 92/22555, WO 97/03988, WO 01/076370, WO 09/004432, U.S. Patent 5,703,078 and U.S. Patent 5,750,695. Generally, the additional active agent(s) is included in the formulations in an amount 25 between about 0.1 µg and about 1000 mg. For example, the amount of the additional active agent or the total amount of the additional active agents (when more than one additional active agent is present) in the formulation is from about 10 µg to about 500 mg, from about 1 mg to about 300 mg, from about 10 mg to about 200 mg, or from about 10 mg to about 100 mg. The term “total amount of the additional active agents” in the formulation refers to the sum of the 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 55 - weight of additional active agents that are not isoxazoline active agents relative to the weight of the formulation. In some embodiments, the additional active agent(s) may be included in the formulations to deliver a dose of from about 5 µg/kg to about 50 mg/kg or from about 0.5 5 mg/kg to about 50 mg/kg per weight of the animal, such as from about 0.01 mg/kg to about 30 mg/kg, from about 0.1 mg/kg to about 20 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, from about 5 µg/kg to about 200 µg/kg, or from about 0.1 mg/kg to about 1 mg/kg of weight of animal. B. Carrier 10 The formulations disclosed herein include a carrier that contains castor oil or a mixture of castor oil and one or more other natural oil(s) (also referred to herein as a “natural oil mixture”). The carrier is alternatively referred to herein as a vehicle, or a vehicle comprising a pharmaceutically acceptable excipient. Typically, the amount of castor oil in the formulation or the natural oil mixture in the formulation is at least 40% (w/w), such as from 40% (w/w) to 15 about 99.9% (w/w). such as from 40% (w/w) to about 99% (w/w), such as from 40% (w/w) to about 95% (w/w), from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 75% (w/w), from 40% (w/w) to about 70% (w/w), from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). 20 Castor oil is a natural oil from castor beans and contains ricinoleic acid and a variety of other natural components such as phytochemicals, terpenoids, and other fatty acids. In some forms, the castor oil contains up to 99.9% ricinoleic acid. In some forms, the castor oil contains up to 10% of other plant-derived fatty acids. For example, a composition of castor oil is 85-95% ricinoleic acid; 2-6% oleic acid; 1-5% linoleic acid; 0.5-1% α-Linolenic acid; 0.5– 25 1% stearic acid; 0.5-1% palmitic acid; 0.3-0.5% dihydroxystearic acid; and 0.2-0.5% or less other natural components and/or other fatty acids. In some embodiments, the formulation contains castor oil as the only natural oil. When castor oil is the only natural oil in the formulation, the amount of castor oil in the formulation is at least 40% (w/w), such as from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 56 - 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 70% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). In some embodiments, the formulation contains castor oil mixed with another natural oil or more than one other natural oil (i.e., a natural oil mixture). For example, the formulation 5 contains a mixture of castor oil and a second natural oil that is not castor oil. For example, the formulation contains a mixture of castor oil and at least one other natural oil that is not castor oil. When castor oil is in a mixture of natural oils contained in the formulation, the total amount of the natural oil mixture is at least 40% (w/w), such as from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% 10 (w/w) to about 70% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). The total amount of natural oil mixture in the formulation refers to the sum of the weight of the natural oils in the mixture of natural oils relative to the weight of the formulation. The other natural oil(s) that are not castor oil in the formulation can be any suitable 15 natural oil. Examples of natural oils suitable for use in combination with castor oil in the formulation include, but are not limited to, cottonseed oil, linseed oil, corn (maize) oil, coconut oil, palm kernel oil, babassu oil, olive oil, peanut oil, arachis oil, sesame oil, soybean oil, safflower oil, perilla oil, oiticica oil, sunflower oil, gourd oil, grape seed oil, sesame oil, hazelnut oil, apricot oil, macadamia oil, avocado oil, jojoba oil, karite butter, liquid 20 triglycerides of fatty acids containing from 4 to 24 carbon atoms (including but are not limited to medium chain-triglycerides (MCT), such as glycerol triesters of caprylic and capric acid, e.g., Miglyol^® 810, Miglyol^® 812, etc.), purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, 2-octyldodecyl erucate, isostearyl isostearate, a triglyceride of fractionated plant fatty acids with chain lengths of C8 and C10 25 combined with linoleic acid (i.e., caprylic/capric/linoleic triglyceride, e.g., Miglyol^® 818, supplied by IOI Oleo), a glycerin ester of fractionated plant fatty acids with chain lengths of C8 and C10 combined with succinic acid (i.e., caprylic/capric/succinic triglyceride, e.g. Miglyol^® 829 ECO or Miglyol^® 829 supplied by ICI Oleo), propylene glycol diester of saturated plant fatty acids with chain lengths of C₈ and C₁₀, e.g., Miglyol^® 840, propylene 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 57 - glycol esters of saturated plant fatty acids with chain lengths of C8 and C10, e.g., Labrafac^TM,PG, propylene glycol dicaprylate/dicaprate NF (supplied by Gattefosse), propylene glycol esters of any one or more of succinic acid, oleic acid, linoleic acid, and alpha-linolenic acid, fish oil, krill oil, omega 3 oil, omega 6 oil, or a mixture thereof. 5 For example, the formulation contains a mixture of castor oil and cottonseed oil, where the amount of the mixture of castor oil and cottonseed oil is at least 40% (w/w), such as from 40% (w/w) to about 99.9% (w/w), such as from 40% (w/w) to about 99% (w/w), such as from 40% (w/w) to about 95% (w/w), such as from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 10 75% (w/w), from 40% (w/w) to about 70% (w/w), from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). C. Pharmaceutically Acceptable Excipients Optionally, the formulation contains one or more pharmaceutically acceptable excipients, in addition to the castor oil, natural oil, and natural oil mixture. Optionally, the one 15 or more pharmaceutically acceptable excipients are contained in the carrier of the formulation. The one or more pharmaceutically acceptable excipients in the formulation are not castor oil, a natural oil, or a natural oil mixture as described herein. Excipients can be added to the formulation to assist in sterility, stability (e.g., shelf-life), integration, and to adjust and/or maintain viscosity of the formulation. Suitable pharmaceutically acceptable excipients are 20 generally recognized as safe (GRAS) and may be administered to an individual without causing undesirable biological side effects or unwanted interactions. When one or more pharmaceutically acceptable excipients are included in the formulation, the total amount of the pharmaceutically acceptable excipients in the formulation generally range from about 0.01% to about 60%, from about 0.01 to about 50%, from about 0.01 to about 40%, from about 0.01 25 to about 30%, from about 0.01 to about 20%, from about 0.01 to about 10%, from about 0.05% to 60% (w/w), from about 0.05% to 50% (w/w), from about 0.05% to 40% (w/w), from about 0.05% to 30% (w/w), from about 0.05% to 20% (w/w), from about 0.05% to 10% (w/w), or from about 0.05% to 1.0% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 58 - In some embodiments, the formulation does not contain poloxamers, polyethylene glycol (PEG), polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, pseudopoly(amides), poly hydroxy 5 alcanoates, poly hydroxybutyrates, poly hydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), poly(methyl vinyl ether), poly(maleic anhydride), chitin, chitosan, and copolymers, terpolymers, or combinations or mixtures therein including copolymers of polylactides, polycaprolactones, polyglycolides (e.g., poly(lactide-co- glycolide) (PLGA) and copolymers of polyethylene glycol or methoxy polyethylene glycol 10 with one or more of polycaprolactone, polylactide or any of the other polymers mentioned above. In some embodiments, the formulation does not contain PLGA, poloxamer, or PEG. Examples of PLGAs, poloxamers, and/or PEGs that can be excluded from the formulation are: PLGA (50:50) (e.g., PLGA (50:50) MW approximately 52 kDa, PLGA (50:50) MW 15 approximately 9 kDa), PLGA (75:25) (e.g., PLGA (75:25) MW approximately 111-115 kDa), poloxamer 124, poloxamer P-181, poloxamer P-188, poloxamer P-237, poloxamer P338, poloxamer P407, and liquid PEG. In some embodiments, the formulation does not contain PLGA, poloxamer, or liquid PEG. A “liquid PEG” refers to a polyethylene glycol with a molecular weight less than 600 Da. 20 Representative categories of excipients suitable for use in the formulations include, but are not limited to, viscosity modifiers, emulsifiers, solubilizers, preservatives, antioxidants, wetting agents, tonicity agents, and stabilizing agents, and combinations thereof. Optionally, the carrier of the formulation contains one or more viscosity modifiers, one or more emulsifiers, or one or more solubilizers, or a combination thereof. 25 Examples of viscosity modifiers suitable for use as pharmaceutically acceptable excipients in the formulation include, but are not limited to, ethyl oleate, ethanol, propylene glycol, and oleic acid, and mixtures thereof. In some embodiments, the viscosity modifiers in the formulation may be or may be in combination with a thickener, including but not limited to, guar gum, alginic acid, gelatin, pectin, agar, and carrageenan, and mixtures thereof. When 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 59 - viscosity modifiers are included in the formulation, the amount of the viscosity modifiers in the formulation generally ranges from about 0.01% to about 30%, from about 0.01% to about 20%, from about 0.1% to about 30%, from about 0.1% to about 20%, from about 0.1% to about 10%, from about 1% to about 30%, from about 1% to about 20%, from about 1% to 5 about 10%, from about 5% to about 30%, from about 5% to about 20%, from about 10% to about 30%, from about 10% to about 20%, from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to 1.0% (w/w). Examples of emulsifiers suitable for use as pharmaceutically acceptable excipients in the formulation include, but are not limited to, lecithin, hydrogenated phosphatidylcholine, 10 glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters, sorbitan esters including sorbitan monooleate (Span^® 20), polysorbates including polysorbate 20 and polysorbate 80, d- α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium lauryl sulfate, polyethylene glycol castor oil derivatives including polyoxyl 35 castor oil (Cremophor^® EL), polyoxyl 40 hydrogenated castor oil (Cremophor^® RH 40), polyoxyl 60 hydrogenated castor oil 15 (Cremophor^® RH60); propylene glycol monolaurate (LAUROGLYCOL^®); glyceride esters including glycerol caprylate/caprate (CAPMUL^® MCM), polyglycolized glycerides (GELUCIRE^®), PEG 300 caprylic/capric glycerides (Softigen^® 767), PEG 300 oleic glycerides (Labrafil^® M-1944CS), PEG 300 linoleic glycerides (Labrafil^® M-2125CS); polyethylene glycol stearates and polyethylene glycol hydroxy stearates including polyoxyl 8 20 stearate (PEG 400 monostearate), polyoxyl 40 stearate (PEG 1750 monostearate, and the like); polyethylene glycol stearates (synonyms include macrogol stearates, polyoxylstearates, polyoxyethylene stearates, ethoxylated stearates; CAS No. 9004-99-3, 9005-08-7) are mixtures of mono- and distearate esters of mixed polyoxyethylene polymers; and polyethylene glycol hydroxystearate, such as polyethylene glycol 12-hydroxystearate. For example, in 25 certain embodiments, the invention according to present disclosure provides formulations containing one or more emulsifiers, such as propylene glycol monocaprylate (Capryol^®, e.g., Capryol^® 90), caprylocaproyl polyoxyl-8 glycerides (Labrasol^®), or polysorbate, or a combination thereof. When emulsifiers are included in the formulation, the amount of the emulsifiers in the formulation generally ranges from about 0.01% to about 50%, from about 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 60 - 0.01% to about 40%, from about 0.1% to about 50%, from about 0.1% to about 40%, from about 1% to about 50%, from about 1% to about 40%, from about 10% to about 50%, from about 10% to about 40%, from about 20% to about 50%, from about 20% to about 45%, from about 0.01% to about 30%, from about 0.01% to about 20%, from about 0.01 to about 10%, 5 from about 0.01 to about 5%, or from about 0.05% to 1.0% (w/w). Examples of solubilizers suitable for use as pharmaceutically acceptable excipients in the formulation include, but are not limited to, glycerol formal, glycofurol, glycerol, propylene glycol, propylene carbonate, sulfobutyl ether cyclodextrin, hydroxypropyl cyclodextrin, cyclodextrins, sorbitan monooleate, benzyl benzoate, lecithin, and hydrogenated 10 phosphatidylcholine, and combinations thereof. For example, in one embodiment, the formulation contains one or more solubilizers, such as glycerol formal, glycofurol, or glycerol, or a combination thereof. In some embodiments, the solubilizer(s) in the formulation can also function as an emulsifier (e.g., amphiphilic excipients, such as glycerol formal) and optionally can also function as a viscosity modifier, such as by reducing the overall viscosity of the 15 formulation. This can occur when the solubilizer(s) have a lower viscosity than castor oil or a natural oil mixture (such as glycerol formal). When solubilizer(s) are included in the formulation, the amount of the solubilizer(s) in the formulation generally ranges from about 0.01% to about 60% (w/w), such as from about 0.01 to about 50% (w/w), from about 0.01 to about 40% (w/w), from about 0.01 to about 30% (w/w), from about 1 to about 60% (w/w), 20 from about 5 to about 60% (w/w), from about 10 to about 60% (w/w), from about 20 to about 60% (w/w), from about 30 to about 60% (w/w), from about 40 to about 60% (w/w), from about 15 to about 50% (w/w), from about 20 to about 50% (w/w), from about 15 to about 40% (w/w), from about 15 to about 35% (w/w), from about 15 to about 30% (w/w), from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to about 1.0% (w/w), 25 such as from about 15 to about 35% (w/w), e.g., about 25% (w/w). Examples of antioxidants suitable for use as pharmaceutically acceptable excipients in the formulation include, but are not limited to, vitamin E, vitamin E TPGS, L-cysteine, L- methionine, sodium bisulfite, sodium sulfate, alpha tocopherol, ascorbic acid, ascorbyl palmitate, citric acid, fumaric acid, malic acid, sodium ascorbate, sodium metabisulfate, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 61 - sodium metabisulfite, n-propyl gallate, BHA (butylated hydroxy anisole), BHT (butylated hydroxy toluene), BHA and citric acid, monothioglycerol, and tert-butyl hydroquinone (TBHQ). When antioxidants are included in the formulation, the amount of the antioxidants in the formulation generally ranges from about 0.01 to about 5.0%, from about 1.0 to about 5 5.0%, from about 2.0 to about 5.0%, from about 3.0 to about 5.0%, and from about 4.0 to about 5.0%, from about 0.01% to about 3%, from about 0.01 to about 2%, or from about 0.05% to 1.0% (w/w). Examples of preservatives suitable for use as pharmaceutically acceptable excipients in the formulation include, but are not limited to, parabens (methylparaben and/or 10 propylparaben), benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butylparaben, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, methylparaben, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium propionate, sorbic acid, and thimerosal. When preservatives are 15 included in the formulation, the amount of the preservatives in the formulation generally ranges from about 0.01 to about 10%, from about 0.01 to about 5%, from about 0.01 to about 1%, from about 0.1 to about 10%, from about 0.1 to about 5%, from about 0.1 to about 1%, from about 1% to about 10%, from about 1% to about 5%, from about 2% to about 10%, from about 2% to about 5%, from about 5 to about 10%, from about 0.01 to about 2.0%, such as 20 from about 0.05 to about 1.0% (w/w). In some embodiments, in addition to castor oil or a natural oil mixture (e.g., a mixture of castor oil and another natural oil, such as any one of those described above, e.g., cotton seed oil and/or glycerol triesters of caprylic and capric acid, such as Miglyol^® 812 and Miglyol^® 840), the formulation also contains ethyl oleate or ethanol; optionally propylene 25 glycol monocaprylate (Capryol^®, e.g., Capryol^® 90), caprylocaproyl polyoxyl-8 glycerides (Labrasol^®), or polysorbate, or a combination thereof; optionally glycerol formal, propylene carbonate, glycofurol, or glycerol, or a combination thereof; and optionally BHA, where the amount of each component in the formulation can be any one of those described above. In some embodiments, the formulation contains BHA. In some embodiments, the formulation 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 62 - contains glycerol formal at a concentration of at least 15% (w/w) or at least 20% (w/w), such as about 25% (w/w). More specific exemplary formulations are described in the Examples below. D. Forms of the Injectable Formulation 5 The formulations disclosed herein are in a form suitable for injection directly into the blood stream, into muscle, or into an internal organ of an animal. Suitable routes for such parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, epidural, intracerebroventricular, intraurethral, intrasternal, intracranial, intramuscular, and subcutaneous delivery. Suitable means for parenteral administration include needle (including 10 microneedle) injectors, needle-free injectors, and infusion techniques. For example, the formulation is in a form suitable for subcutaneous administration. The injectable formulation for parenteral administration is an oil solution or an oil suspension, and may contain excipients such as viscosity modifiers, emulsifiers, and/or solubilizers as described above, and, for some applications, they may be suitably formulated 15 as a sterile solution/suspension. In some embodiments, the injectable formulation is in the form of an oil solution. When in the form of an oil solution, the injectable formulation typically contains one or more solubilizers and/or one or more emulsifiers, and the parasiticidal isoxazoline active agent(s) are dissolved in the castor oil or the mixture of natural oils containing castor oil and one or 20 more other natural oils in the presence of the solubilizer(s) and/or emulsifier(s). For example, the carrier of the injectable formulation contains castor oil or a natural oil mixture containing castor oil and one or more other natural oils, and one or more solubilizers and/or one or more emulsifiers, and the parasiticidal isoxazoline active agent(s) are dissolved in the carrier. For example, the injectable formulation is in the form of an oil solution, where the 25 carrier also contains the following component(s): one or more of glycerol formal, glycofurol, glycerol, and propylene carbonate; and/or one or more of propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, and polysorbate. For injectable formulations in the form of an oil solution, as described herein, the parasiticidal isoxazoline active agent(s) can be dissolved in a carrier that contains one or more of the above-listed component(s). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 63 - In some embodiments, the injectable formulation is in the form of an oil suspension. In these embodiments, the parasiticidal isoxazoline active agent(s) are in the form of particles, where the particles are suspended in the carrier, which contains castor oil or a natural oil mixture containing castor oil and one or more other natural oils. Generally, the isoxazoline 5 particles have an average diameter ranging from about 0.1 nm to about 250 microns, from about 0.1 nm to about 200 microns, from about 0.1 nm to about 150 microns, from about 0.1 nm to about 100 microns, from about 0.1 nm to about 50 microns, from about 0.1 nm to about 10 microns, from about 0.1 nm to about 1 micron, from about 0.1 nm to about 500 nm, from about 0.1 nm to about 100 nm, from about 1 nm to about 250 microns, from about 1 nm to 10 about 200 microns, from about 1 nm to about 150 microns, from about 1 nm to about 100 microns, from about 1 nm to about 50 microns, from about 1 nm to about 10 microns, from about 1 nm to about 1 micron, from about 1 nm to about 500 nm, from about 1 nm to about 100 nm, from about 10 nm to about 250 microns, from about 10 nm to about 200 microns, from about 10 nm to about 150 microns, from about 10 nm to about 100 microns, from about 15 10 nm to about 50 microns, from about 10 nm to about 10 microns, from about 10 nm to about 1 micron, from about 100 nm to about 250 microns, from about 100 nm to about 200 microns, from about 100 nm to about 150 microns, from about 100 nm to about 100 microns, from about 100 nm to about 50 microns, from about 100 nm to about 10 microns, from about 100 nm to about 1 micron, from about 1 micron to about 250 microns, from about 10 microns to 20 about 250 microns, from about 20 microns to about 250 microns, from about 25 microns to about 250 microns, from about 50 microns to about 250 microns, from about 75 microns to about 250 microns, from about 25 microns to about 200 microns, from about 25 microns to about 150 microns, from about 25 microns to about 100 microns, from about 5 microns to about 250 microns, from about 5 microns to about 200 microns, from about 5 microns to about 25 150 microns, from about 5 microns to about 100 microns, from about 5 microns to about 50 microns. In some embodiments, the injectable formulations, either as an oil solution or an oil suspension, are physically stable (e.g., no clumping in the formulation is observed by visual inspection for at least 1 month) at standard ambient temperature and pressure, and thus can be 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 64 - provided as a ready-to-use form without reconstitution or additional preparation step (e.g., combining the components and mixing/shaking the combined components, to form the formulation) prior to injection. The ready-to-use injectable formulation can be provided in a suitable container for sterility, such as a box, blister, vial, bottle, syringe, sachet, ampoule or in 5 any other suitable single-dose or multi-dose holder or container. In some embodiments of the invention according to the present disclosure, polysorbate, preferably polysorbate 20, is a component of the oil suspensions to insure that the components do not settle out of the formulation prior to use and form a cake at the bottom of the vial, bottle, or ampoule container, as the case may be. Polysorbate 20 in the suspension formulations of the invention 10 according to the present disclosure also functions to re-suspend the formulation upon shaking of the container so that the components of the formulation are uniformly dispersed. In some embodiments, the components of the injectable formulation may be provided separately in a kit, such that a user can combine them to form the formulation prior to injection. For example, the parasiticidal isoxazoline active agent(s) is provided in a first 15 container as a dry form; the castor oil or a mixture of castor oil and another natural oil or other natural oils is provided in a second container; and optionally one or more pharmaceutically acceptable excipient(s) is provided in a third container, which are combined to form the injectable formulation by a user prior to injection. Optionally, the pharmaceutically acceptable excipient(s) is provided in the same container as the castor oil or natural oil mixture. 20 Optionally, one or more of the pharmaceutically acceptable excipient(s) is in a dry form and is provided in the same container as the parasiticidal isoxazoline active agent(s). The kit may further contain instructions for use, e.g., mixing and/or administration of the formulation. Suitable first containers for the powder include but are not limited to blister packs, vials, and bottles. Suitable second containers for the castor oil or natural oil mixture include but are not 25 limited to vials, bottles, etc. Optionally, the kit further includes an adaptor that facilitates transfer and/or administration of the pharmaceutical formulation, such as a vial adaptor (open or closed), a syringe (with or without a needle attached thereto), and/or a needle configured for attachment to the syringe for injection. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 65 - E. Properties The performance of the injectable formulations can be evaluated by their properties, such as physical stability, pharmacokinetic (PK) profile, efficacy against parasites, and irritation at injection site. 5 In some embodiments, the injectable formulations disclosed herein are featured with one or more of the following: high physical stability (e.g., no clumping in the formulation for at least 1 month by visual inspection), low irritation at the injection site (e.g., an ISR score ≤ 2 for dogs), favorable plasma isoxazoline concentration at extended time following injection (e.g., a plasma isoxazoline concentration ≥ 30 ng/mL in dogs at 180 days following injection), 10 and prolonged efficacy against parasites (e.g., at least 75% effective against ticks and/or at least 75% effective against fleas for at least 4 months, such as at least 5 months or 6 months). In some embodiments, the injectable formulations disclosed herein have one or more, two or more, or all of the features described above, i.e., high physical stability, low irritation at the injection site, favorable plasma isoxazoline concentration at extended time following 15 injection, and prolonged efficacy against parasites. 1. Physical Stability Typically, the formulations according to the invention of the present disclosure are physically stable at standard ambient temperature and standard ambient pressure, for example, having no clumping in the formulation for at least 1 month by visual inspection. For example, 20 the formulations are physically stable at standard ambient temperature and standard ambient pressure for at least 1 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year. The physical stability of the formulations allows them to be provided as a ready-to-use formulation to users, without reconstitution or other additional steps (e.g., combining the components and mixing/shaking the combined components) to prepare the 25 formulation prior to injection. 2. Pharmacokinetic (PK) Profile Typically, the formulations disclosed herein have a favorable PK profile, as indicated by a favorable mean isoxazoline plasma concentration at extended time following injection. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 66 - The mean isoxazoline plasma concentration at extended time following injection can be measured by methods known in the art, such as LC-MS/MS. For example, plasma samples from dosed dogs are harvested and analyzed by LC-MS/MS and data set acceptability was based on standard curves and fortified QC sample results. More specific methods are 5 described in the Examples below. For example, the formulations disclosed herein have an average plasma isoxazoline concentration of at least 30 ng/mL, such as at least 35 ng/mL, at least 40 ng/mL, at least 45 ng/mL, at least 50 ng/mL, at least 60 ng/mL, from about 30 ng/mL to about 1000 ng/mL, from about 30 ng/mL to about 900 ng/mL, from about 30 ng/mL to about 800 ng/mL, from about 30 10 ng/mL to about 700 ng/mL, from about 30 ng/mL to about 600 ng/mL, from about 30 ng/mL to about 500 ng/mL, from about 30 ng/mL to about 400 ng/mL, from about 30 ng/mL to about 300 ng/mL, from about 30 ng/mL to about 200 ng/mL, from 30 ng/mL to about 100 ng/mL, from 30 ng/mL to about 90 ng/mL, from 30 ng/mL to about 80 ng/mL, from about 45 ng/mL to about 1000 ng/mL, from about 45 ng/mL to about 900 ng/mL, from about 45 ng/mL to 15 about 800 ng/mL, from about 45 ng/mL to about 700 ng/mL, from about 45 ng/mL to about 600 ng/mL, from about 45 ng/mL to about 500 ng/mL, from about 45 ng/mL to about 400 ng/mL, from about 45 ng/mL to about 300 ng/mL, from about 45 ng/mL to about 200 ng/mL, from 45 ng/mL to about 100 ng/mL, from 45 ng/mL to about 90 ng/mL, or from 45 ng/mL to about 80 ng/mL, from about 60 ng/mL to about 1000 ng/mL, from about 60 ng/mL to about 20 900 ng/mL, from about 60 ng/mL to about 800 ng/mL, from about 60 ng/mL to about 700 ng/mL, from about 60 ng/mL to about 600 ng/mL, from about 60 ng/mL to about 500 ng/mL, from about 60 ng/mL to about 400 ng/mL, from about 60 ng/mL to about 300 ng/mL, from about 60 ng/mL to about 200 ng/mL, or from 60 ng/mL to about 100 ng/mL, at day 180-220 following administration, in dogs, optionally measured by LC-MS/MS. 25 3. Efficacy Typically, the formulations disclosed herein have a prolonged efficacy against parasites. The efficacy of the formulations is determined by live tick/flea counts and calculating arithmetic means of the live flea/tick count on the animal. Protocol for counting the live tick/flea counts and calculating arithmetic means of the live flea/tick count on the 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 67 - animal is known, see, for example, WO 2016/138339, Example 23 relating to a counting method used for dogs. In some embodiments, the formulations disclosed herein are at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective at killing parasites for at 5 least 4 months, at least 5 months, at least 6 months, at least 9 months, or from 6 months to 1 year. For example, the formulations disclosed herein are at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective against ticks and/or fleas for at least 4 months, such as at least 5 months or at least 6 months. 10 For example, the formulations disclosed herein are at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective against ticks and/or fleas for at least 4 months, such as at least 5 months or at least 6 months, or from 6 months to 1 year. 4. Irritation at Injection Site Optionally, the formulations disclosed herein show low irritation at the injection site 15 following injection, optionally for an extended time following injection, such as at least 1 month, at least 2 months, at least 3 months, or at least 6 months following injection. The irritation at the injection site of an animal can be determined by observing the tissue reaction at the injection site, such as the appearance and/or the size of nodule(s) at and/or near the injection site; redness, induration (hardness), and/or swelling of the tissue at/or 20 near the injection site; pain and/or itchiness at and/or near the injection site, etc. A variety of scoring systems known in the art can be used for evaluating the injection site reaction of the animal being treated. For example, a scoring system for evaluating injection site reaction can be based on observation of tissue thickening and/or size of nodule at the injection site of the animal. For example, a scoring system for evaluating injection site reaction can be based on 25 pain and/or itchiness at and/or near the injection site of the animal. For example, a scoring system for evaluating injection site reaction can be based on redness, induration, and/or swelling at and/or near the injection site of the animal. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 68 - The specific scoring system may be selected based on the species of the animal being treated. The scores that are considered “Acceptable” using a given scoring system depend on the specific scoring system used and the species of the animal. For example, the following scoring system can be used for evaluating the injection site 5 reaction (ISR) in dogs: ISR score 0 = no detectable tissue reaction (Acceptable); ISR score 1 = thickening of injection site, no distinct nodule (non-fluctuant) (Acceptable); ISR score 2 = small nodule < 2 cm in diameter (Acceptable); 10 ISR score 3 = medium nodule 2 – 3 cm in diameter; ISR score 4 = large nodule > 3 cm in diameter; ISR score 5 = abscess formation; ISR score 6 = pain on palpation, where the term “non-fluctuant” means that the thickened injection site does not move around 15 upon touching or palpation. The exemplary scoring system described above may be used for evaluating the ISR of other animals, as well. However, the specific upper limit of ISR score that is considered “Acceptable” varies depending on the specific species of animals. For example, animals having a smaller size than dogs, such as rats, have a smaller nodule size as the upper limit for 20 Acceptable ISR score, such as a nodule that is < 1 cm in diameter. In some embodiments, the formulations disclosed herein have an ISR score of 2 or lower in dogs, as determined using the exemplary scoring system described above. In some embodiments, the ISR scores of the formulations in dogs are lower than the suspension disclosed in WO 2019/091936 A1, determined using the same scoring system, such as by 25 using the exemplary scoring system described above. For example, exemplary formulations BE, BF, BG, and BH described in the Examples below have a lower ISR score (i.e., smaller nodules/swelling sizes) compared to at least formulations 1A and 1F disclosed in WO 2019/091936 A1, as determined using the same scoring system and the same animal type, but at a significantly longer time point following injection (about 6 months for BE, BF, BG and 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 69 - BH vs. 20-21 days for 1A and 1F in WO 2019/091936 A1), which demonstrate lower irritation of the formulations disclosed herein at the injection site. In some embodiments, the formulations disclosed herein have an ISR score that is lower than a comparative formulation, where the ISR score is determined using the same 5 scoring system and the same animal species. A comparative formulation refers to a formulation of the same isoxazoline active agent at the same concentration and the same carrier and other components at the same concentrations, but does not contain at least 40 wt% of castor oil or a natural oil mixture. For example, the formulations disclosed herein have an ISR score that is lower by at least 1 grade, by at least 2 grades, by at least 3 grades, or by at 10 least 4 grades than a comparative formulation as determined using the same scoring system, such as a grading scale for animals similar to the current FDA toxicity grading scale that is used for humans, and the same animal species. For example, when erythema/redness, induration/swelling, and/or a nodule are observed at the injection site of a formulation described herein, the average diameter of the area/size of the erythema/redness, 15 induration/swelling, and/or nodule is at least 10% smaller, at least 20% smaller, at least 30% smaller, at least 40% smaller, at least 50% smaller, or at least 75% smaller than a comparative formulation, as determined using the same animal species. More specific exemplary formulations and efficacies thereof are described in the Examples below. 20 II. Methods of Use The disclosed formulations are suitable for use in treating or preventing infestation or infection by a broad spectrum of parasites, in an animal in need thereof. The term “treating” or “treat”, or “treatment” are intended to mean the administration of a long-acting formulation to an animal that has a parasitic infestation for the eradication of the parasite or the reduction of 25 the number of the parasites infesting the animal undergoing treatment. It is noted that the formulation may be used to prevent such a parasitic infestation or infection. The terms “prevent”, “prevention” or “prophylaxis” are intended to mean the administration of the long- acting formulation to the animal before the parasitic infection or infestation has occurred to keep said infection or infestation from occurring. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 70 - In one aspect, the invention according to the present disclosure provides a method for treating or preventing parasites (i.e., treating or preventing a parasite infection and/or infestation) in an animal comprising administering a long-acting injectable isoxazoline formulation as described herein to the animal, especially a non-human animal. 5 In one embodiment, the invention according to the present disclosure provides a method for treating or preventing parasites in a dog and/or cat comprising administering a long-acting injectable isoxazoline formulation as described herein to the dog and/or cat. In one embodiment, the invention according to the present disclosure provides a method for treating or preventing parasites in an animal comprising administering to the 10 animal a long-acting injectable formulation comprising: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and 15 the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides a method for treating or preventing parasites in a dog comprising administering to the dog a long-acting injectable formulation comprising: i. at least one parasiticidal isoxazoline active agent; and 20 ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides a25 method for treating or preventing parasites in a cat comprising administering to the cat a long- acting injectable formulation comprising: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 71 - wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides for a method for treating or preventing parasites in an animal comprising administering to the 5 animal a long-acting injectable formulation comprising: i. at least one parasiticidal isoxazoline active agent according to any one of formulae I-VI: 10 wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; 15 R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁶; each R² is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, 20 C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, C₂-C₄ alkoxycarbonyl, —CN or —NO₂; each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁- 25 C6 alkylamino, C2-C6 dialkylamino, —CN or —NO2; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 72 - R⁴ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with 5 one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and 10 C1-C2 alkoxy; each R⁶ is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C₁-C₆ alkylsulfonyl, —CN or —NO₂; each R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3- 15 C₆ cycloalkylamino, C₂-C₇ alkylcarbonyl, C₂-C₇ alkoxycarbonyl, C₂-C₇ alkylaminocarbonyl, C3-C9 dialkylaminocarbonyl, C2-C7 haloalkylcarbonyl, C2-C7 haloalkoxycarbonyl, C2-C7 haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; or Q²; each R⁸ is independently halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁- 20 C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — NO₂; each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 25 alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C2-C6 dialkylamino, —CN, —NO2, phenyl or pyridinyl; R¹⁰ is H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one of more halogen; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 73 - R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R¹² is H; Q³; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more 5 substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and 10 C1-C2 alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; 15 each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or R₁ A₁ 20 Y wherein: R₁ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted 25 with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 74 - haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO2; X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of 5 halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; A₁ is oxygen; and A₂ is oxygen, NR₂ or CR₇R₈; 10 G is G-1 or G-2; B B₂ B1, B2, B3, B4 a Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, 15 haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; or Y is Y-1, Y-2, Y-3, Y-4, 20 Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13;

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 75 - 1₃ ₄ , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R10S(O)-, R10S(O)2-, R10C(O)-, R10C(S)-, R10R11NC(O)-, R10R11NC(S)- R10OC(O)-; 5 R₄, R₅ and R₆ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R₇ and R₈ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 10 R9 is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, 15 R₇C(O)NR₈-, -CN or -NO₂; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 76 - R10 together with R11 form =O, =S or =NR2; or R₁₂ together with R₁₃ form =O, =S or =NR₂; W is O, S or NR2; n is 1-4; and 5 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F₃C H CF₃ or a ph 10 or a p F₃C 1 O -T wherein R¹, R² an p y , , ; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 77 - S Y is the diradical group _nd T is a C1-C6-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl 5 portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y B 3b wherein: Y is hydrogen, fluoro, chloro or bromo; 10 R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a cyclopentyl 15 ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 20 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 78 - In another aspect, the invention according to the present disclosure provides a long- acting injectable formulation as described herein for use in treating or preventing a parasitic infestation or infection in an animal. In one embodiment, the invention according to the present disclosure provides a long- 5 acting injectable formulation as described herein for use in treating or preventing a parasitic infestation or infection in a dog. In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation as described herein for use in treating or preventing a parasitic infestation or infection in a cat. 10 In yet another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for use in treating or preventing a parasitic infestation or infection in a dog wherein the long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second 15 natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for use in treating or preventing a parasitic infestation or 20 infection in cat wherein the long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and 25 the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for use in treating or preventing a flea and/or tick infestation in a dog wherein the long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 79 - ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 5 In another embodiment, the invention according to the present disclosure provides a long-acting injectable formulation for use in treating or preventing a flea and/or tick infestation in a cat wherein the long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second 10 natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In one aspect, the invention according to the present disclosure provides for use of a long-acting injectable formulation as described herein in the preparation of a medicament for 15 treating or preventing a parasitic infestation or infection in an animal. In one embodiment, the invention according to the present disclosure provides for use of a long-acting injectable formulation as described herein in the preparation of a medicament for treating or preventing a parasitic infestation or infection in a dog. In one embodiment, the invention according to the present disclosure provides for use 20 of a long-acting injectable formulation as described herein in the preparation of a medicament for treating or preventing a parasitic infestation or infection in a cat. In another embodiment, the invention according to the present disclosure provides for use of a long-acting injectable formulation as herein described in the preparation of a medicament for treating or preventing a parasitic infestation or infection in a dog, wherein the 25 long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 80 - wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides for use of a long-acting injectable formulation as herein described in the preparation of a 5 medicament for treating or preventing a parasitic infestation or infection in a cat wherein the long-acting injectable formulation comprises: i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, 10 wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). In another embodiment, the invention according to the present disclosure provides for use of a compound according to any one of formulae I-VI: 15 wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ 20 and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more substituents 25 independently selected from R⁶; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 81 - each R² is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or —NO2; 5 each R³ is independently H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1- C₆ alkylamino, C₂-C₆ dialkylamino, —CN or —NO₂; R⁴ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ 10 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C₄-C₇ alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring 15 containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and C₁-C₂ alkoxy; each R⁶ is independently halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ alkylthio, C₁-C₆ 20 alkylsulfinyl, C1-C6 alkylsulfonyl, —CN or —NO2; each R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₃- C6 cycloalkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylaminocarbonyl, C3-C9 dialkylaminocarbonyl, C2-C7 haloalkylcarbonyl, C2-C7 haloalkoxycarbonyl, C2-C7 25 haloalkylaminocarbonyl, C₃-C₉ dihaloalkylaminocarbonyl, hydroxy, —NH₂, —CN or —NO₂; or Q²; each R⁸ is independently halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1- C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 82 - haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — NO₂; each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 5 alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C2-C6 dialkylamino, —CN, —NO2, phenyl or pyridinyl; R¹⁰ is H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one of more halogen; 10 R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; R¹² is H; Q³; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or 15 R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C₁-C₂ alkoxy; 20 Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each 25 ring optionally substituted with one or more substituents independently selected from R⁹; Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 83 - R₁ A₁ N Y wherein: R1 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, 5 halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO₂; 10 X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; A1 is oxygen; and 15 A2 is oxygen, NR2 or CR7R8; G is G-1 or G-2; B₂ B₁, B₂, B₃, B₄ an a e epe e y o - ; 20 Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 84 - each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; or Y is Y-1, Y-2, Y-3, Y-4, 5 Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13; R₂ R₁₂ R₁₃ R₂ N^R R 2^R3 OR₂ R_{2 12} R₁₃ _N N 4 , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R₁₀S(O)-, R₁₀S(O)₂-, R₁₀C(O)-, R₁₀C(S)-, R₁₀R₁₁NC(O)-, R₁₀R₁₁NC(S)- R₁₀OC(O)-; 10 R4, R5 and R6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R7 and R8 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 15 R₉ is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 85 - cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R7C(O)NR8-, -CN or -NO2; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, 5 alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or R10 together with R11 form =O, =S or =NR2; or R12 together with R13 form =O, =S or =NR2; W is O, S or NR₂; n is 1-4; and 10 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F C H CF₃ or a pharmaceutically acceptable salt thereof; or 15 Formula (IV) or a pharmaceutically acceptable salt thereof; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 86 - -T wherein R¹, R² an S Y is the diradical group _nd 5 T is a C₁-C₆-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y 3b 10 wherein: Y is hydrogen, fluoro, chloro or bromo; R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; 15 R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 87 - R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for use in treating or preventing infestation by 5 fleas and/or ticks, wherein the medicament is in the form of a long-acting injectable formulation comprising a compound according to any one of formulae I-VI or a pharmaceutically acceptable salt thereof and a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% 10 (w/w). Examples of parasites that can be prevented and/or treated using the disclosed method include, but are not limited to, fleas, ticks, mites, mosquitoes, flies, blowflies, lice, cestodes, nematodes, and hookworms and roundworms of the digestive tract of animals and humans, and combinations thereof. 15 The animal being treated can be either wild or domesticated, such as livestock and companion animals, for example, cats, dogs, horses, birds including chickens, sheep, goats, pigs, deer, turkeys, and cattle. Generally, the method for treating or preventing parasites includes administering to the animal the formulation described herein. The formulation is injected into the animal, such as 20 intramuscular administration, intravenous administration, intraperitoneal administration, or subcutaneous administration, such as subcutaneous injection. In some embodiments, the disclosed method does not include a reconstitution or preparation (e.g., combining the components and mixing/shaking the combined components) step to form the formulation prior to administration. 25 The formulation is administered to the animal in an amount that is at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing the infestation and/or infection by the parasite (e.g., fleas and/or ticks, such as Ctenocephalides felis, Amblyomma Americanum, Rhipicephalus sanguineus, Ixodes scapularis, Dermacentor variabilis, Dermacentor reticulatus, Ixodes Ricinus, Ixodes 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 88 - holocyclus, and/or Haemaphysalis longicornis) for at least 6 months, such as from 6 months to 1 year, following a single administration to the animal. The term “a single administration” means administration of the pharmaceutical formulation to an animal within a time period of 24 hours (e.g., within 12 hours, within 2 hours, within 1 hour, etc.), where the administration 5 can be performed at one site or more than one site of the animal. When the pharmaceutical formulation is administered at more than one site of the animal, such as two sites of the animal, in a single administration, the administration at the different sites can be performed simultaneously or sequentially. The specific site of administration and the number of sites for administration depend on the specific infestation and/or infection, the specific parasites, the 10 type of the animal (e.g., breed, size, overall health condition, etc.), the dose/volume of the pharmaceutical formulation, etc. For example, a dog is injected at two sites in a single administration to separate out a dose of 7 mL of the pharmaceutical formulation, where 3 mL of the pharmaceutical formulation is administered on the left shoulder (subcutaneous fat) of the dog, and 4 mL of the 15 pharmaceutical formulation is administered on the right shoulder of the dog, as subcutaneous space of the dog can accommodate ~5-6 mL of the pharmaceutical formulation. Following the single administration in the left and right shoulders of the dog, the formulation administered to the dog is in an amount that is at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing the infestation and/or infection by 20 the parasite (e.g., fleas and/or ticks) for at least 6 months. For example, the formulation is administered to the animal (e.g., cat, dog, equine, swine, bovine, or ovine) in an amount that is at least 75% effective, at least 80% effective, at least 85% effective, at least 90% effective, such as 100% effective, at treating or preventing infestation by fleas and/or ticks, for at least 6 months following a single administration to the 25 animal. For example, the formulation is administered to the animal (e.g., cat or dog) in an amount that is at least 75%, at least 80% effective, at least 85% effective, at least 90% effective, such as 100% effective, at treating or preventing infestation by fleas and/or ticks, for at least 6 months following a single administration to the animal. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 89 - For example, the formulation is administered to the animal (e.g., dog) in an amount that is at least 75% effective, at least 80% effective, at least 85% effective, at least 90% effective, such as 100% effective, at treating or preventing infestation by fleas and/or ticks, for at least 6 months following a single administration to the animal. 5 In some embodiments, the administration step can be repeated regularly or irregularly as needed. Administration of the long-acting formulation at a suitable interval, such as every 6 months or every year may effectively prevent new parasitic infestations or infections in animals by killing new parasites that attack an animal before they can multiply to establish an infestation or infection. 10 Optionally, the formulation is administered to the animal (e.g., cats and/or dogs) in an amount that is at least 75% effective, at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing the infestation and/or by the parasite (e.g., infestation by fleas and/or ticks) for at least 6 months, optionally during which the irritation at the injection site is minimal (e.g., an ISR score ≤ 2 for dogs as determined using the exemplary 15 scoring system described above and in the Examples). Generally, the dose of isoxazoline active agent(s) in the formulation administered to the animal that is effective against at treating or preventing infestation and/or infection by the parasite is in a range from about 0.1 to about 50 mg per kg of body weight, from about 0.5 to about 30 mg/kg, from about 0.5 to about 30 mg/kg body weight, from about 0.5 to about 20 20 mg/kg, from about 0.5 to about 10 mg/kg, from about 0.5 to about 5 mg/kg body weight, from about 0.5 to about 2.5 mg/kg body weight, from about 10 to about 30 mg/kg, from about 15 to about 30 mg/kg, or from about 20 to about 30 mg/kg of body weight of the animal, following a single administration, where the single administration may be performed at one site of the animal or more than one site of the animal, such as two sites of the animal, within a time 25 period of 24 hours. The disclosed formulations and methods can be further understood through the following numbered paragraphs. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 90 - Paragraph 1. A long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent; and 5 ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 10 Paragraph 2. The long-acting injectable formulation of Paragraph 1, wherein the at least one parasiticidal isoxazoline active agent has a structure of: wherein: 15 A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl 20 or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁶; each R² is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, C₂-C₄ 25 alkoxycarbonyl, —CN or —NO2; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 91 - each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C₃-C₆ halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1- C6 alkylamino, C2-C6 dialkylamino, —CN or —NO2; 5 R⁴ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C₄-C₇ alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or 10 R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and C1-C2 alkoxy; 15 each R⁶ is independently halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ alkylthio, C₁-C₆ alkylsulfinyl, C1-C6 alkylsulfonyl, —CN or —NO2; each R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ alkylamino, C₂-C₈ dialkylamino, C₃- C₆ cycloalkylamino, C₂-C₇ alkylcarbonyl, C₂-C₇ alkoxycarbonyl, C₂-C₇ alkylaminocarbonyl, 20 C3-C9 dialkylaminocarbonyl, C2-C7 haloalkylcarbonyl, C2-C7 haloalkoxycarbonyl, C2-C7 haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; or Q²; each R⁸ is independently halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1- C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C625 haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, C₂-C₄ alkoxycarbonyl, —CN or — NO2; each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 92 - alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C₂-C₆ dialkylamino, —CN, —NO₂, phenyl or pyridinyl; R¹⁰ is H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one of more 5 halogen; R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; R¹² is H; Q³; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more 10 substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and 15 C₁-C₂ alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; 20 each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or R₁ A₁ 25 Y 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 93 - Formula (II) wherein: R1 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted 5 with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO₂; X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of 10 halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; A1 is oxygen; and A2 is oxygen, NR2 or CR7R8; 15 G is G-1 or G-2; B₂ B₁, B₂, B₃, B₄ an Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, 20 haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; or Y is Y-1, Y-2, Y-3, Y-4, 25 Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 94 - 1₃ ₄ , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R10S(O)-, R10S(O)2-, R10C(O)-, R10C(S)-, R10R11NC(O)-, R10R11NC(S)- R10OC(O)-; 5 R₄, R₅ and R₆ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R₇ and R₈ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 10 R9 is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, 15 R₇C(O)NR₈-, -CN or -NO₂; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 95 - R10 together with R11 form =O, =S or =NR2; or R₁₂ together with R₁₃ form =O, =S or =NR₂; W is O, S or NR2; n is 1-4; and 5 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F₃C H CF₃ or a ph 10 or a p F₃C O -T o u a wherein R¹, R² and R³ are independently H, Cl, F or CF₃; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 96 - S Y is the diradical group _nd T is a C1-C6-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl 5 portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y B 3b wherein: Y is hydrogen, fluoro, chloro or bromo; 10 R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a 15 cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof; or a combination thereof. Paragraph 3. The long-acting injectable formulation according to Paragraph 2, wherein the at least one isoxazoline compound is a compound of formula (I), or a pharmaceutically acceptable 20 salt thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 97 - Paragraph 4. The long-acting injectable formulation according to Paragraph 3, wherein in the at least one isoxazoline active agent is a compound of the formula (Ib): N R5 5 or a pharmac , wherein R² independently is halogen, C1-C6 alkyl or C1-C6 haloalkyl R⁴ is H or C₁-C₆ alkyl; 10 R⁵ is C1-C4 alkyl optionally substituted with one or more R⁷; and R⁷ is C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylaminocarbonyl, C3-C9 dialkylaminocarbonyl, C₂-C₇ haloalkylcarbonyl, C₂-C₇ haloalkoxycarbonyl, C₂-C₇ haloalkylaminocarbonyl, C₃-C₉ dihaloalkylaminocarbonyl; and n is 0, 1 or 2. 15 Paragraph 5. The long-acting injectable formulation of claim Paragraph 4, wherein the at least one parasiticidal isoxazoline active agent has a structure of: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 98 - F₃ or a pharmaceutic 5 Paragraph 6. The long-acting injectable formulation of Paragraph 5, wherein the at least one parasiticidal isoxazoline active agent has a structure of: O ^N O F₃ or a pharmaceutically acceptable salt thereof. 10 Paragraph 7. The long-acting injectable formulation of any one of Paragraphs 1-6, wherein the carrier further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of a viscosity modifier, preferably selected from one or both of ethyl oleate and ethanol; an emulsifier, preferably selected from one or more of the group 15 consisting of propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, and polysorbate; a solubilizer, preferably selected from one or more of the group consisting of glycerol formal, glycofurol, glycerol, and propylene carbonate; an antioxidant, a preservative, or a combination thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 99 - Paragraph 8. The long-acting injectable formulation of Paragraph 7, wherein the viscosity modifier is ethyl oleate or ethanol. 5 Paragraph 9. The long-acting injectable formulation of Paragraph 7 or Paragraph 8, wherein the emulsifier is propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, or polysorbate, or a combination thereof. Paragraph 10. The long-acting injectable formulation of any one of Paragraphs 7-9, wherein 10 the solubilizer is glycerol formal, glycofurol, glycerol, or propylene carbonate, or a combination thereof. Paragraph 11. The long-acting injectable formulation of any one of Paragraphs 7-10, wherein the antioxidant is BHA. 15 Paragraph 12. The long-acting injectable formulation of any one of Paragraphs 1-11, wherein the second natural oil is cottonseed oil, linseed oil, corn (maize) oil, coconut oil, palm kernel oil, babassu oil, olive oil, peanut oil, arachis oil, sesame oil, soybean oil, safflower oil, perilla oil, oiticica oil, sunflower oil, gourd oil, grape seed oil, sesame oil, hazelnut oil, apricot oil, 20 macadamia oil, avocado oil, jojoba oil, karite butter, liquid triglycerides of fatty acids comprising from 4 to 24 carbon atoms, medium chain-triglycerides (MCT), glycerol triesters of caprylic and capric acid, purcellin oil, isononyl isononanoate, isopropyl myristate, 2- ethylhexyl palmitate, 2-octyldodecyl stearate, 2-octyldodecyl erucate, isostearyl isostearate, caprylic/capric/linoleic triglyceride, caprylic/capric/succinic triglyceride, propylene glycol 25 diesters of saturated plant fatty acids with chain lengths of C₈ and C₁₀, propylene glycol dicaprylate, propylene glycol esters of any one or more of succinic acid, oleic acid, linoleic acid, and alpha-linolenic acid, fish oil, krill oil, omega 3 oil, or omega 6 oil, or a mixture of any two or more of the second natural oils. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 100 - Paragraph 13. The long-acting injectable formulation of Paragraph 12, wherein the second natural oil is cottonseed oil or a glycerol triester of caprylic and capric acid. 5 Paragraph 14. The long-acting injectable formulation of any one of Paragraphs 1-13, wherein the carrier further comprises one or more solubilizer and/or one or more emulsifier, and wherein the at least one parasiticidal isoxazoline active agent is dissolved in the carrier. Paragraph 15. The long-acting injectable formulation of any one of Paragraphs 1-13, wherein 10 the at least one parasiticidal isoxazoline active agent is in the form of particles, and wherein the particles are suspended in the carrier. Paragraph 16. The long-acting injectable formulation of any one of Paragraphs 1-15, wherein the formulation is physically stable at standard ambient temperature and pressure for at least 1 15 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year. Paragraph 17. The long-acting injectable formulation of any one of Paragraphs 1-16, wherein the formulation does not contain PLGA. 20 Paragraph 18. The long-acting injectable formulation of any one of Paragraphs 1-17, wherein the formulation does not contain poloxamer. Paragraph 19. The long-acting injectable formulation of any one of Paragraphs 1-18, wherein the formulation does not contain PEG. 25 Paragraph 20 The long-acting injectable formulation of any one of Paragraphs 1-19, wherein the amount of the at least one parasiticidal isoxazoline active agent in the formulation is from about 0.1 wt% to about 40 wt%, from about 0.1 wt% to about 35 wt%, from about 0.1 wt% to about 30 wt%, from about 0.1 wt% to about 25 wt%, from about 0.1 wt% to about 20 wt%, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 101 - from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 10 wt%, from about 1 wt% to about 40 wt%, from about 1 wt% to about 35 wt%, from about 1 wt% to about 30 wt%, from about 1 wt% to about 25 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 10 wt%, from about 5 wt% to about 40 wt%, from 5 about 5 wt% to about 35 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 25 wt%, or from about 5 wt% to about 20 wt%, or about 15 wt%, or about 17.5 wt %. Paragraph 21. The long-acting injectable formulation of any one of Paragraphs 1-20, wherein the amount of castor oil or a combination of castor oil and a second natural oil is from 40% 10 (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 75% (w/w), from 40% (w/w) to about 70% (w/w), from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). 15 Paragraph 22. The long-acting injectable formulation of Paragraph 21 wherein the carrier comprises a combination of castor oil and a second natural oil. Paragraph 23. The long-acting injectable formulation of Paragraph 22, wherein the second natural oil is cottonseed oil. 20 Paragraph 24. The long-acting injectable formulation of any one of Paragraphs 1-20, wherein the long-acting formulation does contain not a second natural oil, and the amount of castor oil is from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 75% (w/w), from 40% (w/w) to about 25 70% (w/w), from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). Paragraph 25. The long-acting injectable formulation of any one of Paragraphs 7-24, wherein the amount of the viscosity modifier ranges from about 0.01% to about 30%, from about 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 102 - 0.01% to about 20%, from about 0.1% to about 30%, from about 0.1% to about 20%, from about 0.1% to about 10%, from about 1% to about 30%, from about 1% to about 20%, from about 1% to about 10%, from about 5% to about 30%, from about 5% to about 20%, from about 10% to about 30%, from about 10% to about 20%, from about 0.01 to about 10%, from 5 about 0.01 to about 5%, or from about 0.05% to 1.0% (w/w). Paragraph 26. The long-acting injectable formulation of any one of Paragraphs 7-25, wherein the amount of the emulsifier ranges from about 0.01% to about 50%, from about 0.01% to about 40%, from about 0.1% to about 50%, from about 0.1% to about 40%, from about 1% to 10 about 50%, from about 1% to about 40%, from about 10% to about 50%, from about 10% to about 40%, from about 20% to about 50%, from about 20% to about 45%, from about 0.01% to about 30%, from about 0.01% to about 20%, from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to 1.0% (w/w). 15 Paragraph 27. The long-acting injectable formulation of any one of Paragraphs 7-26, wherein the amount of the solubilizer ranges from about 0.01% to about 60% (w/w), from about 0.01 to about 50% (w/w), from about 0.01 to about 40% (w/w), from about 0.01 to about 30% (w/w), from about 1 to about 60% (w/w), from about 5 to about 60% (w/w), from about 10 to about 60% (w/w), from about 20 to about 60% (w/w), from about 30 to about 60% (w/w), 20 from about 40 to about 60% (w/w), from about 15 to about 50% (w/w), from about 20 to about 50% (w/w), from about 15 to about 40% (w/w), from about 15 to about 35% (w/w), from about 15 to about 30% (w/w), from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to about 1.0% (w/w), or from about 15 to about 35% (w/w), about 20 to about 30% (w/w), or about 25% (w/w). 25 Paragraph 28. The long-acting injectable formulation of any one of Paragraphs 7-27, wherein the amount of the antioxidant ranges from about 0.01 to about 5%, from about 1 to about 5%, from about 2to about 5%, from about 3to about 5%, and from about 4to about 5%, from about 0.01% to about 3%, from about 0.01 to about 2%, or from about 0.05% to 1% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 103 - Paragraph 29. The long-acting injectable formulation of any one of Paragraphs 7-28, wherein the amount of the preservative ranges from about 0.01 to about 10%, from about 0.01 to about 5%, from about 0.01 to about 1%, from about 0.1 to about 10%, from about 0.1 to about 5%, 5 from about 0.1 to about 1%, from about 1% to about 10%, from about 1% to about 5%, from about 2% to about 10%, from about 2% to about 5%, from about 5 to about 10%, from about 0.01 to about 2%, or about 0.05 to about 1% (w/w). Paragraph 30. The long-acting injectable formulation of any one of Paragraphs 1-6, wherein 10 the carrier further comprises: (a) from about from about 0.01% to about 20% (w/w), preferably from about 0.1% to 10% (w/w), of a viscosity modifier; and (b) one or more solubilizers and/or one or more emulsifiers, wherein the at least one parasiticidal isoxazoline active agent is dissolved in the 15 carrier, optionally, wherein the second natural oil is cotton seed oil, optionally, wherein the one or more solubilizers are present in an amount from about 0.01% to about 60% (w/w) or preferably, about 5% to about 30% (w/w) of the long-acting injectable formulation, 20 optionally, wherein the one or more solubilizers comprise glycerol formal, glycofurol, glycerol, or propylene carbonate, or a combination thereof, optionally, wherein the one or more emulsifiers are present in an amount from about 0.01% to about 50% (w/w) or preferably, from about 20% to 45%, (w/w) of the long-acting injectable formulation, and 25 optionally, wherein the one or more emulsifiers are selected from any one or more of the group consisting of propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, and polysorbate. Paragraph 31. The long-acting injectable formulation of Paragraph 30, further comprising 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 104 - from about 0.01 to about 5.0% (w/w) of an antioxidant, preferably butylated hydroxyanisole. Paragraph 32. The long-acting injectable formulation of any one of Paragraphs 30-31, wherein the viscosity modifier is ethyl oleate or ethanol, or a combination thereof. 5 Paragraph 33. The long-acting injectable formulation of any one of Paragraphs 30-32, wherein the solubilizer is glycerol formal or propylene carbonate, or a combination thereof. Paragraph 34. The long-acting injectable formulation of any one of Paragraphs 30-33, 10 wherein the emulsifier is propylene glycol monocaprylate or caprylocaproyl polyoxyl-8 glycerides, or a combination thereof. Paragraph 35. The long-acting injectable formulation of any one of Paragraphs 1-6, wherein the at least one parasiticidal isoxazoline active agent is in the form of 15 particles, and wherein the particles are suspended in the carrier, optionally, wherein the second natural oil is a glycerol triester of caprylic and capric acid, wherein the carrier further comprises: (a) from about from about 0.01% to about 30% (w/w), preferably from about 5% to 20 30% (w/w) of a viscosity modifier; and (b) from about 0.01% to about 5% (w/w), preferably from about 0.1% to 1% (w/w) of an emulsifier. Paragraph 36. The long-acting injectable formulation of Paragraph 35, wherein the viscosity 25 modifier is ethyl oleate. Paragraph 37. The long-acting injectable formulation of any one of Paragraphs 35-36, wherein the emulsifier is polysorbate 20. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 105 - Paragraph 38. A long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent, wherein the at least one parasiticidal active agent has a structure of (Ia) O ^N O F₃ 5 and ii. a carrier comprising castor oil, wherein the amount of castor oil in the formulation is at least 40% (w/w). 10 Paragraph 39. The long-acting injectable formulation of Paragraph 38, wherein the at least one parasiticidal isoxazoline active agent has a structure of (S)-Ia: O F₃ , o a p a aceu ca y accep a e sa e eo . 15 Paragraph 40. The long-acting injectable formulation of any one of Paragraphs 38-39, wherein the carrier further comprises polysorbate 20, Miglyol^® 812N, and ethyl oleate. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 106 - Paragraph 41. The long-acting injectable formulation of any one of Paragraphs 38-40, wherein the at least one parasiticidal isoxazoline active agent is in the form of particles, and wherein the particles are suspended in the carrier. 5 Paragraph 42. The long-acting injectable formulation of any one of Paragraphs 38-39, wherein the carrier further comprises one or more excipients selected from the group consisting of ethanol, ethyl oleate, glycerol formal, propylene carbonate, Capryol^® 90, and Labrasol^®. 10 Paragraph 43. The long-acting injectable formulation of Paragraph 42, wherein one or more excipients are selected from the group consisting of ethanol, ethyl oleate, and glycerol formal. Paragraph 44. The long-acting injectable formulation of any one of Paragraphs 38-39, 15 wherein the carrier further comprises two or three excipients selected from the group consisting of glycerol formal, ethanol and ethyl oleate. Paragraph 45. The long-acting injectable formulation of any one of Paragraphs 1-44, wherein the formulation is at least 80% effective, at least 85% effective, or at least 90% effective at 20 treating infestation by fleas and/or ticks for at least 6 months following a single administration to the animal. Paragraph 46. The long-acting injectable formulation of any one of Paragraphs 1-45, further comprising a second active agent selected from the group consisting of an acaricide, an 25 anthelmintic, an anti-parasitic, and an insecticide. Paragraph 47. The long-acting injectable formulation of any one of Paragraphs 1-46, wherein long-acting indicates that the formulation provides at least 75%, especially at least 80%, preferably at least 85%, ,more preferably at least 90%, even more preferably at least 95%, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 107 - most preferably more than 95% efficacy against ectoparasites, including but not limited to ticks and/or fleas, for at least 3 months, preferably at least 4 months, more preferably at least 5 months, even more preferably at least 6 months, most preferably more than 6 months. 5 Paragraph 48. The long-acting injectable formulation of Paragraph 47 wherein the ectoparasites are fleas. Paragraph 49. The long-acting injectable formulation of Paragraph 47 wherein the ectoparasites are ticks. 10 Paragraph 50. A method for treating or preventing parasites in an animal comprising administering the long-acting injectable formulation of any one of Paragraphs 1-49 to the animal, preferably a non-human animal. 15 Paragraph 51. The method according to Paragraph 50, wherein the long-acting injectable formulation is administered at one site or at more than one site of the animal in a single administration. Paragraph 52. The method according to any one of Paragraphs 50-51, wherein the 20 formulation is at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing infestation by fleas and/or ticks for at least 6 months following a single administration to the animal, Paragraph 53. The method of any one of Paragraphs 50-52, wherein the animal is a cat and/or 25 a dog, especially a dog. Paragraph 54. The method of any one or more of Paragraphs 50-53, wherein the long-acting injectable formulation is administered by subcutaneous injection. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 108 - Paragraph 55. The method of any one of Paragraphs 50-54, wherein the dosage of the parasiticidal isoxazoline active agent administered to the animal is from about 0.1 to about 50 mg per kg of body weight, from about 0.5 to about 30 mg/kg, from about 0.5 to about 30 mg/kg body weight, from about 0.5 to about 20 mg/kg, from about 0.5 to about 10 mg/kg, 5 from about 0.5 to about 5 mg/kg body weight, from about 0.5 to about 2.5 mg/kg body weight, from about 10 to about 30 mg/kg, from about 15 to about 30 mg/kg, or from about 20 to about 30 mg/kg of body weight of the animal. Paragraph 56. The method of any one of Paragraphs 50-55, wherein the animal is a dog and 10 wherein following the administration, the site of injection has an injection site reaction (ISR) score of less than 2, as determined using the average diameter of a nodule formed at the site of injection. Paragraph 57. A long-acting injectable formulation according to any one of Paragraphs 1-49 15 for use in treating or preventing a parasitic infestation or infection in an animal, preferably a non-human animal, especially a cat and/or a dog. Paragraph 58. The long-acting injectable formulation for use according to Paragraph 57, wherein the parasitic infestation is a tick and/or a flea infestation. 20 Paragraph 59. Use of a long-acting injectable formulation according to any one of claims 1- 49 in the preparation of a medicament for treating or preventing a parasitic infestation or infection, preferably treating a parasitic infestation, in an animal, preferably a non-human animal, especially a cat and/or a dog. 25 Paragraph 60. Use of a compound according to any one of formulae I-VI: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 109 - wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ 5 and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents 10 independently selected from R⁶; each R² is independently H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or —NO₂; 15 each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁- C6 alkylamino, C2-C6 dialkylamino, —CN or —NO2; R⁴ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 20 alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring 25 containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 110 - consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C1-C2 alkoxy; each R⁶ is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 5 alkylsulfinyl, C₁-C₆ alkylsulfonyl, —CN or —NO₂; each R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3- C₆ cycloalkylamino, C₂-C₇ alkylcarbonyl, C₂-C₇ alkoxycarbonyl, C₂-C₇ alkylaminocarbonyl, C₃-C₉ dialkylaminocarbonyl, C₂-C₇ haloalkylcarbonyl, C₂-C₇ haloalkoxycarbonyl, C₂-C₇ 10 haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; or Q²; each R⁸ is independently halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁- C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — 15 NO₂; each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, —CN, —NO₂, phenyl or pyridinyl; 20 R¹⁰ is H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one of more halogen; R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; 25 R¹² is H; Q³; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 111 - group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C1-C2 alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered 5 fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; 10 Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or R₁ A₁ N Y 15 wherein: R₁ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, 20 haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO2; X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, 25 R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 112 - A1 is oxygen; and A₂ is oxygen, NR₂ or CR₇R₈; G is G-1 or G-2; B₃ B B₂ 5 B1, B2, B3, B4 a Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, 10 alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; or Y is Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13;

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 113 - 1₃ ₄ , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R10S(O)-, R10S(O)2-, R10C(O)-, R10C(S)-, R10R11NC(O)-, R10R11NC(S)- R10OC(O)-; 5 R₄, R₅ and R₆ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R₇ and R₈ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 10 R9 is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, 15 R₇C(O)NR₈-, -CN or -NO₂; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 114 - R10 together with R11 form =O, =S or =NR2; or R₁₂ together with R₁₃ form =O, =S or =NR₂; W is O, S or NR2; n is 1-4; and 5 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F₃C H CF₃ or a ph 10 or a p F₃C O -T o u a wherein R¹, R² and R³ are independently H, Cl, F or CF₃; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 115 - S Y is the diradical group _nd T is a C1-C6-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl 5 portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y B 3b wherein: Y is hydrogen, fluoro, chloro or bromo; 10 R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a 15 cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof; in the preparation of a medicament for use in treating or preventing infestation by fleas and/or ticks, wherein the medicament is in the form of a long-acting injectable formulation comprising a compound according to any one of formulae I-VI and a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the 20 formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 116 - Paragraph 61. A kit for preparing a composition for treating or preventing infestation by fleas and/or ticks according to Paragraph 2, wherein the kit comprises a) an isoxazoline active agent having a structure of any one of formulae I-VI , or a 5 pharmaceutically acceptable salt thereof; b) a vehicle comprising a pharmaceutically acceptable excipient capable of forming a suspension or solution with said isoxazoline agent; and c) instructions for combining said isoxazoline active agent with the vehicle. 10 Paragraph 62. The kit of Paragraph 61, wherein the parasiticidal isoxazoline active agent has a structure of I(a): F₃ , 15 Paragraph 63. The kit of Paragraph 62, wherein the isoxazoline compound has a structure of (S)-Ia: F₃ , or a pharmaceutically acceptable salt thereof. 20 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 117 - Paragraph 64. A process for preparing a ready to use long-acting injectable formulation according to any one of Paragraphs 1-49 wherein the process comprises: a) providing at least one isoxazoline active agent; b) providing a carrier comprising castor oil or a combination of castor oil and a second natural 5 oil; c) combining the at least one isoxazoline active agent and the carrier in a container to provide a long-acting injectable formulation, and d) mixing the long-acting injectable formulation in the container for a period of time according to instructions provided with the at least one isoxazoline agent. 10 Paragraph 65. The process according to Paragraph 64, wherein said isoxazoline active agent is a compound that has a structure of I(a): O O F₃ , , 15 and wherein the amount of castor oil or combination of castor oil and a second natural oil in said formulation is at least 40% (w/w). Paragraph 66. The process according to Paragraph 65, wherein said isoxazoline active agent is a compound that has a structure of (S)-Ia:

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 118 - F3 , EXAMPLES 5 Example 1. Exemplary Long-Acting Injectable Formulations and Efficacies Thereof Materials and Methods Exemplary long-acting injectable formulations were prepared by mixing the components as shown in Tables 1-5 below. Amorphous form esafoxolaner was used for the solution-based formulations listed in 10 Tables 1, 2, and 4. The suspension-based formulations listed in Tables 3 and 5 contain esafoxolaner in crystalline polymorphic forms I and II (“Form I” or “Form II"). Esafoxolaner is disclosed in Patent Nos. US 7,964,204 and US 8,410,153 and can be obtained by a process such as that disclosed in WO 2017/176948 A1, all of which are incorporated herein by reference in their entireties. Crystalline forms I and II of esafoxolaner, 15 i.e., (S)-afoxolaner, can be obtained by a process such as that disclosed in WO 2018/187623 A1, which is incorporated herein by reference in its entirety. A rat model was utilized to provide comparative pharmacokinetic (PK) profile and injection site reaction (ISR) observations for the formulations shown in Table 1. The formulations were administered as 0.1 mL injection via subcutaneous route. The rats were 20 bled, and the injection sites were observed for at least 3 months (90 days). A beagle dog model was utilized to provide comparative PK profile and ISR observations in canine for the formulations (Tables 2 and 3). PK Profile Measurement BH: Plasma samples were harvested and analyzed with the following method: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 119 - Method Type LC-MS/MS Analyte(s) esafoxolaner a Acceptabi C sample results. BE, BF, and BG: Plasma samples from esafoxolaner dosed dogs were harvested and analyzed with the following method: Method LC-MS/MS r 5 Pharmacokinetic paramet rtmental approach consistent with the extravascular rou te of administration [Phoenix 64 WinNonlin 8.1]. ISR observations The following scoring system was used for evaluating the ISR in dogs: ISR score 0 = no detectable tissue reaction; 10 ISR score 1 = thickening of injection site, no distinct nodule (non-fluctuant); ISR score 2 = small nodule ≤ approx. ≤ 0.5 – < 2 cm in diameter – considered Acceptable; ISR score 3 = medium nodule approx. 2 – 3 cm in diameter; ISR score 4 = large nodule > 3 cm in diameter; 15 ISR score 5 = abscess formation; ISR score 6 = pain on palpation. In the rat studies, ISR scores 1 and below were deemed Acceptable, due to the smaller size of rats compared to dogs. Further, dogs were subjected to experimental parasite infestation challenge to elucidate 20 esafoxolaner efficacy at select time points (Tables 4 and 5). The formulations were administered at the desired volume per kg body weight via subcutaneous route. The dogs were bled, and the injection sites were observed for at least 6 months (180 days). To determine 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 120 - efficacy of these formulations, tick/flea counts were performed and arithmetic means of the live flea/tick count were calculated. Results Rat Studies 5 Table 1 shows the components of oil solution-based formulations, PK profiles, and descriptions of the size of the irritation in cm and the duration of the irritation at the injection sites of rats. ISR score 1 and below were deemed acceptable. As shown in Table 1, oil solution-based formulations containing castor oil achieved favorable results in rat model. For example, oil solution-based formulations that contain castor 10 oil, such as formulation I (containing 9.2% w/w API (active pharmaceutical ingredient, i.e., esafoxolaner) in castor oil and Capryol 90) and formulation W (containing 10.29% w/w API in castor oil and glycerol formal), achieved esafoxolaner plasma concentration of 51.1 ng/mL and 73.1 ng/mL, respectively, at the end of the study day 92. In contrast, oil solutions that do not contain castor oil, such as formulation J (containing 9.2% w/w API in Labrasol and 15 Miglyol 812N), formulation X (containing 9.73% w/w API in Capryol 90, cottonseed oil and soybean oil), formulation AF (containing 8.04% w/w API in caprylic acid and ethyl oleate) and formulation AG (containing 7.51% w/w API in capric acid and caprylic acid) showed unfavorable esafoxolaner plasma concentration at the end of study day 92. In this study, an esafoxolaner plasma concentration of less than 30 ng/mL at day 92 or longer is considered to 20 be unfavorable. Formulation J was below limit of quantification (BLOQ) even on day 72, formulation X achieved 19.3 ng/mL at end of the study day 92, formulation AF achieved 6.42 ng/mL at the end of the study day 92, and formulation AG was BLOQ even on day 70. Further, it is surprising that castor oil or castor oil mixed with other natural oils (such as cottonseed oil) at levels ≥ 40% in the solution blend can achieve optimal esafoxolaner 25 plasma levels at the end of the study day 92. For example, administration of oil solution-based formulations containing ≥ 40% castor oil content, such as formulation H (containing 9.9% w/w API in 47.3% castor oil), formulation I (containing 9.2% w/w API in 53.1% castor oil), formulation W (containing 10.29% w/w API in 69.21% castor oil), formulation AN (containing 12.5% w/w API in 56.5% castor oil), and formulation AO (containing 15% w/w 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 121 - API in 50.98% castor oil), provided an extended release of 39.4 ng/mL, 51.1 ng/mL, 73.1 ng/mL, 95.5 ng/mL and 112 ng/mL plasma esafoxolaner concentration, respectively, at the end of study (either day 92 or day 105). Oil solution-based formulation containing ≥ 40% mixture of castor oil and natural oil, such as formulation AH (containing 9.99% w/w API in 5 38.39% castor oil, 31.23% cottonseed oil and 0.5% curcumin), also yielded an extended release of 43.1 ng/mL plasma esafoxolaner concentration at the end of the study day 112. In contrast, administration of formulations containing < 40% castor oil content, such as formulation G (containing 10% w/w API in 29% castor oil) and formulation V (containing 9.98% w/w API in 19.19% castor oil), yielded an esafoxolaner plasma concentration BLOQ 10 and 11.2 ng/mL, respectively, at the end of the study day 92. Dog Studies Formulations that yielded favorable extended esafoxolaner plasma release in the rat model were further evaluated in dog studies. 15 As shown in Table 2 and Table 4, oil solution-based formulations provided prolonged release of esafoxolaner for more than 6 months with proven efficacy against ectoparasite infestation and/or infection, such as efficacy against fleas and ticks. Similar to the surprising observations in the rat studies, oil solution-based formulation containing ≥ 40% castor oil provide controlled release of esafoxolaner for more than 6 months. 20 For example, as shown in Table 2, formulations containing ≥ 40% castor oil, such as formulation BE (containing 10.45% w/w API in 40.17% castor oil), formulation BF (containing 10.61% w/w API in 50.95% castor oil), and formulation BG (containing 9.9% w/w API in 47.3% castor oil), yielded 46.2 ng/mL, 80.4 ng/mL, and 50.8 ng/mL, respectively, at the end of the study day 184. Further, as shown in Table 4, formulations BE, BF, and BG 25 achieved an efficacy of >75% against fleas (C. felis) infestation challenge after 6 months from administration. These results demonstrate that oil solution-based formulation containing ≥ 40% castor oil or castor oil mixed with other natural oils can achieve prolonged plasma esafoxolaner longevity and efficacy against ectoparasites for more than 6 months. In contrast, formulation containing < 40% castor oil, such as formulation BB (containing 9.98% w/w API 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 122 - in 19.19% castor oil), yielded an unfavorable plasma esafoxolaner concentration of 27.8 ng/mL at the end of the study day 182. Other oil solution-based formulations with higher API concentration may further boost plasma esafoxolaner levels after 6 months. For example, as shown in Table 2 and Table 4, 5 formulation BH (containing 14.2% w/w API in 55.8% w/w castor oil) achieved an esafoxolaner plasma concentration of 63.5 ng/mL at the end of the study day 204 and protected dogs from fleas (C. felis) and ticks (R. sanguineus and A. amblyomma) with >75% efficacy after 6 months from administration. Formulation BD (containing 20.84% w/w API in 40.05% castor oil) achieved an esafoxolaner plasma concentration of 98.7 ng/mL at the end of 10 the study day 189, and protected dogs from fleas (C. felis) and ticks (R. sanguineus and A. amblyomma) with >75% efficacy after 6 months from administration. Oil suspension-based formulations containing castor oil were also prepared and tested. For example, as shown in Table 3, oil suspension-based formulations containing polysorbate 20, medium chain triglyceride (Miglyol 812N), ethyl oleate, castor oil, and esafoxolaner in 15 either its crystalline polymorphic form I (“Form I”), such as formulation BI (containing 9.4% w/w API), or its crystalline polymorphic form II (“Form II”), such as formulation BJ (containing 9.2% w/w API), achieved plasma esafoxolaner concentration of 49.7 ng/mL and 87.3 ng/mL, respectively, at the end of the study day 204. Further, as shown in Table 5, both oil suspension-based formulations BI and BJ yielded >75% efficacy against flea (C. felis) and 20 tick (R. sanguineus and A. amblyomma) infestation challenges after 6 months from administration. These results demonstrate that oil suspension-based formulations containing castor oil, regardless of the polymorphic forms of esafoxolaner, can achieve satisfactory controlled release to achieve at least 6 months of pharmaceutically relevant effect to control and prevent infestation of ectoparasites. 25 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 123 - _s noⁱ _t ^a _l u ^m _r o F _e vⁱ _t ^a _r ap mo ^C dna_s noⁱ _t ^a _l u ^m _r o ^F noⁱ _t ^u _l o ^e ₎ ^Sl _s _i o ^. _l o L 1_. ¹ _. ^{1 1 1} ^O D V ^m ₍ 0 0 _. 0 _. 0 _. 0 ^y _r ^w ^a _/ ⁴ _{4 l} _l 9 % _, o _{, ,} p w ,_l 1 _, ^l _i ⁸ _{. ,} ^l _i 09 ^{, n} _a ^, _l ⁰ _9l ^l _i o ^m % _{e , ,} ^l _i ^o x n n o _s M a _l o_r ^0, _l o_{r l l} o _l ^o _{s l} o ^h _t ^o _s o _r _r ⁱ _f ^{o o} _s ^y _r o ^{a y} _l ^{E a} _r ^y _r ^o _tE oⁱ _t oⁱ _{t r} ^a _{r t} s^{a o} _t s^{p n} _r g % ^b _a ^p _a ^s _a A_f ^a _l ⁱ _s ^o _t ^b ^s _a ^b _{a a r a a a} h_t ^b _{a i} 3^{. L C C} H o _s u o _a ^e _i d ^m p ^{L C b} r ^C _{a l} o ^{C C L M} ₇ ^B m % ^L ⁵ % % ^{L E} _, % % % 3ⁿ _a % 1 % 5 % % 6 % 9 N 3 5 0 3 9 1 %5 ^u _t o o % F C 9 _. 2 35 ⁵ _. S _. 7 C 7 % 4 2 ^h 4 _{t . .} E 35 03 ² _{. . .} 2 _{. . .} 7 93 34 18 24 82 91 ¹ _. S 0 _t a R ¹.x _. ^{o .} _c ^w _/ % ¹ _f a_s no w % % 9 % % 8 ^e _l E C % 01 _. ² _. ² _. ⁹ _. b 9 9 9 9 a T ^D _I G H _{I J} V 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 124 - m ⁽ ^e _{s 9} o ² _{. 3} D 01 ⁷ _{4 1} _. 9 ⁰ _. 8 ⁵ _. 7 e_s ^. _{l )} o o L D V ^m ₍ ¹ _. 0 ¹ _. 0 ¹ _. 0 ¹ _. 0 , A _, n _{, ,} ^, _{e ,} l_i o _l H ⁰ ₉ ^d _e ^a _e ^d _i ^{* t} b ^c _{a * a} ^d _i c n e A ,_r ^o _r ^B _l o ^e _s n y A _c 0 ^e ⁸ _l o _{a c e} _c ⁱ _l w H n n ^o _t ^e _c % %5 ^y _r o o S H ⁱ _l n _l y ⁱ _r ^y _r ^{T B} oⁱ _t o^{i s} _a ^y _l 2 ¹ _. ^p _a ^t _t o ^{B y} _r ^e _e ^h _t A ^p _a ^p _a % a _t _l ⁱ _s ^{C G 1} _. ^{0 C C} %4 % ^p _a w ^E H % C^C 4 5 u o ⁸ % % _, ^, _l o % % ⁸ _. 5 ^{C T} % ^B % % ⁵ _. ¹ _. 0 m p ^w _/ 1 8 ^l _a ⁿ _a 6 7 71 ¹ _. 0 0 % % 8 % 1 4 _{, ,} _r m ₎ o o w ² _. 9 ³ _. 2 ^m _r ⁷ _. ⁶ _{. , ,} ⁴ _. 8 ⁹ _. 5 ⁰ _. ⁹ _. ^{d *} _* o^h _t 6 5 ^l _i ^l _i 3 ⁵ _. 7 ¹ _. 0 1 _i c 0 ^d _e F C % 6 1 _f E 3 3 o o 6 0 2 0 2 7 _a 8unⁱ _t ¹. n x ^o _c ^o _f ^. _c ^w _/ %9 % % % ^{( a} _s no w ² _. 3 7 4 1 ¹ E C % 01 _. 9 ⁰ _. 8 ⁵ _. 7^e _l ba F G T ^D _I W X A A 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 125 - - 1.x o_f a_s E n a_e n a_e g m ^e _l ^c ⁽ b ¹ wo a - 5_. n e_{s 9} ⁵ _t c^{0 k} o ⁹ _{. . 5 e} ^{. o} _s D 9 21 1 ^t _{e x} ^l ^d o o ^r _a n _{p s} p ⁱ 0 e_s o ^. _{l )} o L ^{= a 8} ^{0 ≤} n e D V ^m ₍ ¹ _. 0 ¹ _. 0 ¹ _. 0 ^e _r ^e _l o u _e d w w_{/ l c} o T , A A A ^s n l_i ^o _{r , l *} w ^d _e H H H R ^* ^{e e} _c ^B _, ^l _l ^l _{i l} ^S _I ^l _{a .} % n _, o_{r s} n ^y _l 8 _i n ^o _t o % 8 % o 5 _r ^o _r ^B o ^o ^e _c % % _{r r} ^B m ^r _e 5 ^o _t ^e _c % % _* 5 _; ^{s t} _e oⁱ _t oⁱ _t ^s _a ^t _t ^G o 0 ^. ₇ % ^o ⁵ _{. ,} ¹ _{. t} s 4 4 ^r _e ⁼ m a ^y _l ⁹ _. ¹ _. ^s _a ^y _l ⁹ _. ¹ _. n ^{2 a} _i ₎ ^a _l ⁱ _s ^{C C} 1 ⁰ _, ⁿ _i ^0, _l ^{G 3} _, ^0, _l ^{C G 3} _, ^0, _l ^a _l ^e _r ^d ^d _e u o u p %9 % ⁰ _. 3 2 ^l _a mu o ^C % ^l _a o % % ^l _a o ox ^o _c n ⁱn ^m ⁱ _{t r} m ³ _. ² _. 1_, ^c _r ⁿ _a % 5_. 6 0_. ⁿ _a 8 9 7 0ⁿ _a ^o _f ^s mn o o 8 1 ^l _i ^m _r o u ^h _t 6 7 ^m _r o^h _{t .} 0 _. 0 ^m _r ^h _t ^a _s R ^c ^o F C 3 3 o _f C E 5 2 _f E 5 3 ^o _f E _c ^{E S} _I ²- ⁽ 1 = _; ⁾ _t 1 > ¹ _{. .} x x ⁿ _{a .} ^e _l ^. _c ^o _f u x b ^o _f n ^w _/ %9 % 5_. ^a _s ^t _c ^o _r a ^a T _s o w E C % ⁹ _. 9 2 % 1 51 ₁ ^E u p l _f ^p _a D _I H N O A A A 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 126 - _s noⁱ _t ^a _l n u ^a _e ^m _r M o F _evⁱ _t ^a _r ap mo ^C dna _s noⁱ _t ^a _l u ^m _r o ^F d ^e _s a ^B-n oⁱ _s _t o ^u _l o L 2 _l ^{m 1} 2 . ¹ 2 . ¹ _. ^u D V ₍ 0 0 0 o ^Sl _{i ,} ^, ^l _l ,^o _l % ^O _{, r a l} o _r ^, _l o _s o 5 ^y _r n n ^o _t ^a _l o ^{s m} _r ⁿ ⁱ o t ⁱ _{t a} C %8 ^o _{f a} ^o _t ^a ^s _, ⁿ l ^h A _{a r} ^y t ^b _r ¹ ^p _. 0 H _a C % 0 7 9 ^h A t H _{a a} L % _, 9 ^l _i p ^a _l ⁱ _s ^{3 E B} _l ^{E B C} o ^m _e u op % _. ^o _r 1 2 ^e % % % ⁰ _. o 5 0 ^y % % % ¹ _. 9 _r x ^m _r m ^w _/ E o o w ² _. 1_{, c} F C % 96 ^l 2 5 i ^y _l o G ¹ _. 8 ¹ _. ⁹ _. 3_{, r} 0 05 ^l _i ^p _a 7 % o C ³ 5 3 0 1 ^o _t A . 8 ¹ _. ⁵ _. ³ _{. ,} ^s _a H 0 24 8 0 _f 2 9 C B o _s ^e _, _i ^r _e n d ^u n ^o _i _t ^a _l ^t _a ^S o ^r _t g x n o ^o _f ^{e w} %9 %1 % a _{c /} _s n w ² _. ⁶ _. 8 D_. ² E ^o _c % 01 01 ⁹ _. 9 ^e _l b A B a ^D T _I W B B 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 127 - g e_s ^k _/ o L W D m B ¹ _. 0 e _r n %2 n _, o n i_t o ^o _t i _, ^e _l y ² _. %5 t ^s _a %0 p ^{8, 1} _. a_l ⁱ _s ^C 2 9 u o ⁶ _{. l} ^o _{r e} o ^{P t} _a ^0, _l p ^w %4 ^y n o m_r m_/ 5 2_{, r} %7 o ⁿ _a A o o w ⁰ _. ^{l p} _a ^{2 b} _r ^h _t H F C % 04 _i o C _. 6 ^a _c E B , r n _{) e} o ^d _e n ⁱ ^a _t _l a un o ^r ⁱ _t x _t n n ^{o e w} _/ %4 ^o _{f c} _c ^a ⁽ _s n w ⁸ ^o _. 0 ² E _c % 2 ^e _l b ^D D a T _I B 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 128 - B^B g g e g s ^k o _/ ^m g ⁵ _. ^k _/ 2 g ⁵ _. W ⁵ _. D m 1 m 21 B 21 g 5 g k 5 g k 5 g e_s ^k _/ 2 _/ 2 _/ 2 ^k _/ o g W ¹ L W ¹ L W ¹ L W D m B _. 0 m B _. 0 m B _. 0 m B n _{, r} o n ^o _r _t ^o _r % i_t o^{i s} _{a , t} 0 A ^s _{a ,} 0 A ^o _t ⁸ _. 0 A a _t % l ⁱ _s ^C 8 9_l H ^C %7 9_l H ^s _a ^, _l H u o mp r m ^w _/ %³ _. o ^B 7 9 %⁰ _. o ^, _l o ^{B C} %^o _s ^, _l o ^B w ¹ _. 4_, ^y _r % 5 0 p 5 ⁹ _. 3_, ^y _r %ⁿ % %2 ^a ^p 7 _a 5 ³ _. 4_{, r} ⁿ % b _a 5 o o F C % 04 ^l _{i a} o C ¹ _. 0 05 ^l _{i a} o C ³ _. ^h _t 8 E ¹ _. 0 74 ^l _{i a} ^h _t o L E ¹ _. 0 , n ₎ ^r _e o ^d n ⁱ _t _e ^a a u _l n o ^r _t ⁱ _t x n % % n ^o ^o _f ^e _c ^w _/ 5 _c ^a ⁽ _s n w ⁴ _. 1 % E ^o _c % 0 ⁶ _. 1 01 ⁹ _. 9 ² ^e _l b ^D E F G a T _I B B B 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 129 - l n a_e M n L a x ^{, m} _a _e a ₀ 4 _e ^p m ^m _/ 6 ^t _i ⁼ M C g n 1 ^s n ^{3 =} ^o _i ^e ^t _r ⁶ c ^o _c ^e _r e g s₎ ^e _j ^{s o} _c n_i R ^s o ^k _/ g W ₅ D 1 _f ^S _I R m _; ₍ B ^{o S} g ^e _I n _{l ;} _i b n_e ^a n t p ^o _i ^t _a _e k e g ^c _i ^e _c _s m ^{k m} o ^u _{l / ) 6} L W 0 h 1_. ^{t c} _{a r} _e ^o _f D o B V ^m ₍ 0 ⁼ ^{1 b} _s s ^e o _e _r ^{t .} ^{o d c} _{s 0} 2 w _{, c e} b a _e ^t / ^l _{a .} ^s m s_. R ^{e =} _a b n w ^m _r ^{q S} _{e r} _I ^{d 5 o} _s oⁱ _t %_, ^o _f ^, _{e ;} ^{– e} _r _l ^t _a ^l _i no ^r _e ^o _c ^y _l o a_l n ^o _r ^e _l o_r ⁱ _t ^t _e ^{s P} u oⁱ _t ^e O ^o _t ^c _a m R S^s _a m_r ⁱ _{s c} o o ^y _l _l y ^s _a ^e _r ^a _{i I; e} p ^{G h} _t C _e ^d n ^r _e m F m ^{E u} _s ^{i t a} _s o % ^s _{i e} m _e C 5 % 2 5 ^t ^e _l ^c m a_i ^h _t b ^{2 d} _s r _, ^a _t ^< n ⁱ e n ^c 0 e^{t – i} ⁵ _. m ² n ₎ n oⁱ _e ^{c e} ^d _e _e ^a _{l t} a ^w _/ % ^{d 0} o ^{≤ 3} ^> w u o n x ^r _t w ² _. ^{n .} ⁱ _x _t ^o _f n ^e ^e 4 _l ^T _. _c % 1 ⁼ o^{r u} 0 n _c ^a _s ⁰ _{p d} 8 ^o n ^e ⁽ E ^o _{c r} p o a n _e ^t _a ^{2 o} _c ^≤ _e g ^b _r ^e _l ^{s e} _l ^r _a ^o _s b H R u ^l a ^D _I B ^S _I d ^y _l T _* o n ⁼ 4 o P 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 130 - *n ² _n ^{i l} _l o _n ² _n ^{i l} _l o _n e_s ^e _s m ^k _{/ ) 6} ^t a o ^u _l o L W ¹ _{6 e s} _. ¹ _. ⁼ m ^{> i} B 0 0 ^{1 a} _i ^e _l 0 B- D ^m ₍ ^e u ² n V _r ^d oⁱ _s ^o _c n d n e ^{s i o} _{n e} n_e m _e w p _{e l l l} R ^c g s_, ^t _a o y _{r e l} h^o _t ^t _a o y _r h^o _t ^S _I; ^{2 r} _a ^T ^{l .} ₀ u n n ^b _r ^y _{l t} ^{s b} _r ^y _{l t} ^{s <} 8 S o l_i ⁱ _t o^{i g} _i ^E _a ^g _i ^E _a no ^{– =} _e ^t ^{O a} _{l t} ⁱ ^y u _s ^w o _/ ^o _s y_l ^M % C 7 _. ^o _s C ⁱ . ^s _. ^l _i ^y _l ^M % 7 _{. t} _. ^s _. ^l _i ^c _a ⁵ _. ⁴ _a b r p w o P % ^{7 q} o o % ^{7 q} o ^{e 0 e} _r o _r o l ⁶ _{. 2} ^{, P 6} _{. 2} ^, _r ^≤ _{. c s} a^m _r m % p o o % ⁸ _{, e} ^{t 8} _{, e e} x ^{s y} _l F C 9 _1, N2 _a % e ₁ _l 9 _, N ^t 2 _a e_l ^u _s s_i ^o _r R o S^P ^m _e ¹ _. 0 02 18 O ¹ _. 0 02 18 O ^{t p} _{p I;} ^{r s} _a x ^e _l E b ^a f ^a _t ^e _{l e} ^t _e u _e m o _{, )} ^{) c} d m ^a _s _s ^r ^e _{i e} n _I n o ^{I I} _e ^t _e on ^a _i d _{; e} d ⁱ _t ^m _r ^m _r d _l ^l n n ^h _t u_t ^a _l o a r^w _/ o o _{o a} ^{i o} _{i s} ⁱ ^S x _t n w F ⁽ F ^{( n} m ^s m c^t _a 0 g ^o _f o ^e _c % ⁼ p ⁸ ^a % % ^{0 = 3 l} _a n D _s n . E ^{o 4} _. ² _. ^e _r ^{2 – p e} _e 3 _c 9 9 ^o _c ^e _r 2 n e_l ^{s o} w c_. s x ^o T o nⁱ _: b _{I J} R _r a ^D _I B B S R p _a p^e _t o T ^I * ^S _I ^p _a = N 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 131 - _e g ⁿ _e ^l _l ah ^C noⁱ _t a^t _s ^e _f n ^I ^e _t ⁱ _s ^a _r a P_l ^a _t ⁿ _e ^m _i ^r _e px ^E ⁿ _i _s noⁱ _t ^a _l u ^m _r o ^F d _s ^e _s o ^u W _. D_l o L B 0 ¹ _. ¹ _. ¹ _. ¹ _. a ^m ₍ 0 0 0 0 ^B V -no _, ⁱ _{l l} _t n ^l o % %2 % o % o _{l i} % o ^u _l ⁱ _t 2 o ⁱ ^S _s ⁶ _. ² _. A 9 2_. ⁿ _a 7 ⁿ o ^{h 0} _{. a} % o 2 ^{n 5} _{, r} o_t ^l _i p ⁴ ₂ % ⁸ H , 7 ^, ^{l 2} _{. e} ^t _a ^{B 9} _{2 t} _, ^{E 0} ₃ ^h _t E 4 _a _, ^h _t ^l _a ^s _a l _, ^l _i ^{E m} _r C ^O m _i o ⁶ % _i o % ^l _i o % o ^o _. ^y o _r ^{C w} _/ w _{r ,} o 0 ⁿ _o 5 5 7 t 9 ^b _r ¹ _r _{. r} o_t ¹ _{. r} ³ ^{8 o} _{t .} 8^o _t % _f ^s ⁸ _. _{. l} o_r ^q ^a _l n ^s _l ^{a 0 s} _, ^s _, ^s _a ^{0 ,} _e p oⁱ _t % _a o _c ^, _{l a} 0 _a 0 ^, ^{C y} _l ^e r_e o ^C 9 ^C 9 ^{C o} _c ^t ^y _a ^m _e ^a _l ^p n ⁿ _{a l l} % _s a _l ^e _l x u % _a ^e _l ^h % o % o ³ _{. r} ^G O E 5 C y _t 7 ^y _r 5 ^y _r 7 ^b _a % _l _f ^m _r ⁰ _. p E ¹ _. ^{p 9} _. ^p 4 5 y ^o o 04 ^o _r 0 _{a a} L 4 05 2 ^h _t ^y _c F P C C E a ^c _i ^f _f ^r _e ^w _/ ^E n _. ^a _l w % % % ⁴ o 4 5 1 % % x ^% ^e _l ^o _f ^{. 2} c ⁸ _. 0 ⁴ _. 0 ⁶ _. 0 ⁹ _{. .} 9 41 ba ^a _s n 2 1 1 o T E _c D _I D E F G H B B B B B 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 132 - f_e g 1₁ _e g ⁿ _e ^l _l ah ^C noⁱ _t a^t _s ^e _f n ^I ^e _t ⁱ _s ^a _r a P_l ^a _t ⁿ _e ^m _i ^r _e px ^E ⁿ _i _s noⁱ _t ^a _l u ^m _r o ^F d ^e _s a ^B-no ^e g s ^k _{/ ) 6 6} ⁱ _s o L W ¹ _. ¹ _. ⁿ D B 0 0 _e ^m ₍ ^p _s u ^Sl _{i e l l} n _, ^t n _a o y _r y_l ^h _t ^o _e _t ^t _{l l r} _a o y y_l ^h _t ^o _t ^O ^y o ^b _r _r ⁱ _t oⁱ _t ^{g s} _a ^b _r ^{g s} _a ^a _l ^a _l ⁱ _s ^w p u o _/ ^o _{s i} ^E ^y _l ^M % C 7 _. ^o _{s i} ^E . ^s _. ^l _i ^y _l ^M % C 7 _. _. ^s _. ^l _i p w o ^m _e ^m _r ^P % 6_. ⁷ ₂ ^q o o % ,^{P 6} _. ⁷ ₂ ^q o , x o m % o % ⁸ _{1 , e} N ^t _a % ⁸ _{1 , e} N ^t _a E F C 9 1_{. ,} 2 ^e _l 9 1_{. ,} 2 ^e _l _f 0 1 O 0 1 ^o 0 2 8 0 2 8 O ^y _c a ^c _{i )} ^f _f ^r _e ^{I )} _I ^E n ^I _. ^a _l ^, _c ^w _/ ^m _r o ^m _r ⁵ ox n ^e _l ^{o o} w F o c ⁽ F ⁽ b _f a_s ^% % 4_. % a T E 9 ² _. 9 D _{I J} _I B B

Claims

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 133 - We claim: 1. A long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: 5 i. at least one parasiticidal isoxazoline active agent; and ii. a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 10 2. The long-acting injectable formulation of claim 1, wherein the at least one parasiticidal isoxazoline active agent has a structure of: 15 wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; 20 R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C₄-C₇ cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁶; each R² is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 134 - C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or —NO₂; each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, 5 C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁- C6 alkylamino, C2-C6 dialkylamino, —CN or —NO2; R⁴ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ 10 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents 15 independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C1-C2 alkoxy; each R⁶ is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C₁-C₆ alkylsulfonyl, —CN or —NO₂; each R⁷ is independently halogen; C₁-C₆ alkyl, C₃-C₆ cycloalkyl, C₁-C₆ alkoxy, C₁-C₆20 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3- C6 cycloalkylamino, C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylaminocarbonyl, C₃-C₉ dialkylaminocarbonyl, C₂-C₇ haloalkylcarbonyl, C₂-C₇ haloalkoxycarbonyl, C₂-C₇ haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; or Q²; 25 each R⁸ is independently halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁- C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — NO₂; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 135 - each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, —CN, —NO2, phenyl or pyridinyl; 5 R¹⁰ is H; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one of more halogen; R¹¹ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; 10 R¹² is H; Q³; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the 15 group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C1-C2 alkyl, halogen, —CN, —NO2 and C1-C2 alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 20 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally 25 substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 136 - R₁ A₁ N Y wherein: R1 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, 5 halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO₂; 10 X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; A1 is oxygen; and 15 A2 is oxygen, NR2 or CR7R8; G is G-1 or G-2; B₂ B₁, B₂, B₃, B₄ an a e epe e y o - ; 20 Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 137 - each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; or Y is Y-1, Y-2, Y-3, Y-4, 5 Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13; R₂ R₁₂ R₁₃ R₂ N^R R 2^R3 OR₂ R_{2 12} R₁₃ _N N 4 , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R₁₀S(O)-, R₁₀S(O)₂-, R₁₀C(O)-, R₁₀C(S)-, R₁₀R₁₁NC(O)-, R₁₀R₁₁NC(S)- R₁₀OC(O)-; 10 R4, R5 and R6 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R7 and R8 are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 15 R₉ is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 138 - cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R7C(O)NR8-, -CN or -NO2; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, 5 alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or R10 together with R11 form =O, =S or =NR2; or R12 together with R13 form =O, =S or =NR2; W is O, S or NR₂; n is 1-4; and 10 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F C H CF₃ or a pharmaceutically acceptable salt thereof; or 15 Formula (IV) or a pharmaceutically acceptable salt thereof; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 139 - -T wherein R¹, R² an S Y is the diradical group _nd 5 T is a C₁-C₆-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y 3b 10 wherein: Y is hydrogen, fluoro, chloro or bromo; R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; 15 R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 140 - R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof; or a combination thereof. 5 3. The long-acting injectable formulation according to claim 2, wherein the at least one isoxazoline compound is a compound of formula (I), or a pharmaceutically acceptable salt thereof. 10 4. The long-acting injectable formulation according to claim 3, wherein the at least one isoxazoline active agent is a compound of the formula (Ib): O ^N R⁵ or a pharmaceutica 15 wherein R² independently is halogen, C1-C6 alkyl or C1-C6 haloalkyl; R⁴ is H or C₁-C₆ alkyl; R⁵ is C1-C4 alkyl optionally substituted with one or more R⁷; and R⁷ is C2-C7 alkylcarbonyl, C2-C7 alkoxycarbonyl, C2-C7 alkylaminocarbonyl, C3-C9 dialkylaminocarbonyl, 20 C₂-C₇ haloalkylcarbonyl, C₂-C₇ haloalkoxycarbonyl, C₂-C₇ haloalkylaminocarbonyl, C₃-C₉ dihaloalkylaminocarbonyl; and n is 0, 1 or 2. 5. The long-acting injectable formulation of claim 4, wherein the at least one parasiticidal isoxazoline active agent has a structure of: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 141 - F₃ or a pharmaceutic 5 6. The long-acting injectable formulation of claim 5, wherein the at least one parasiticidal isoxazoline active agent has a structure of: O ^N O F₃ or a pharmaceutic 10 7. The long-acting injectable formulation of any one of claims 1-6, wherein the carrier further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of a viscosity modifier, preferably selected from one or both of ethyl oleate and ethanol; an emulsifier, preferably selected from one or more of the group consisting of 15 propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, and polysorbate; a solubilizer, preferably selected from one or more of the group consisting of glycerol formal, glycofurol, glycerol, and propylene carbonate; an antioxidant; a preservative; or a combination thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 142 - 8. The long-acting injectable formulation of claim 7, wherein the viscosity modifier is ethyl oleate or ethanol. 5 9. The long-acting injectable formulation of claim 7 or 8, wherein the emulsifier is propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, or polysorbate, or a combination thereof. 10. The long-acting injectable formulation of any one of claims 7-9, wherein the 10 solubilizer is glycerol formal, glycofurol, glycerol, or propylene carbonate, or a combination thereof. 11. The long-acting injectable formulation of any one of claims 7-10, wherein the antioxidant is BHA. 15 12. The long-acting injectable formulation of any one of claims 1-11, wherein the second natural oil is cottonseed oil, linseed oil, corn (maize) oil, coconut oil, palm kernel oil, babassu oil, olive oil, peanut oil, arachis oil, sesame oil, soybean oil, safflower oil, perilla oil, oiticica oil, sunflower oil, gourd oil, grape seed oil, sesame oil, hazelnut oil, apricot oil, macadamia 20 oil, avocado oil, jojoba oil, karite butter, liquid triglycerides of fatty acids comprising from 4 to 24 carbon atoms, medium chain-triglycerides (MCT), glycerol triesters of caprylic and capric acid, purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl stearate, 2-octyldodecyl erucate, isostearyl isostearate, caprylic/capric/linoleic triglyceride, caprylic/capric/succinic triglyceride, propylene glycol diesters of saturated plant 25 fatty acids with chain lengths of C₈ and C₁₀, propylene glycol dicaprylate, propylene glycol esters of any one or more of succinic acid, oleic acid, linoleic acid, and alpha-linolenic acid, fish oil, krill oil, omega 3 oil, or omega 6 oil, or a mixture of any two or more of the second natural oils. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 143 - 13. The long-acting injectable formulation of claim 12, wherein the second natural oil is cottonseed oil or a glycerol triester of caprylic and capric acid. 5 14. The long-acting injectable formulation of any one of claims 1-13, wherein the carrier further comprises one or more solubilizer and/or one or more emulsifier, and wherein the at least one parasiticidal isoxazoline active agent is dissolved in the carrier. 15. The long-acting injectable formulation of any one of claims 1-13, wherein the at least 10 one parasiticidal isoxazoline active agent is in the form of particles, and wherein the particles are suspended in the carrier. 16. The long-acting injectable formulation of any one of claims 1-15, wherein the formulation is physically stable at standard ambient temperature and pressure for at least 1 15 month, at least 2 months, at least 3 months, at least 6 months, or at least 1 year. 17. The long-acting injectable formulation of any one of claims 1-16, wherein the formulation does not contain PLGA. 20 18. The long-acting injectable formulation of any one of claims 1-17, wherein the formulation does not contain poloxamer. 19. The long-acting injectable formulation of any one of claims 1-18, wherein the formulation does not contain PEG. 25 20. The long-acting injectable formulation of any one of claims 1-19, wherein the amount of the at least one parasiticidal isoxazoline active agent in the formulation is from about 0.1 wt% to about 40 wt%, from about 0.1 wt% to about 35 wt%, from about 0.1 wt% to about 30 wt%, from about 0.1 wt% to about 25 wt%, from about 0.1 wt% to about 20 wt%, from about 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 144 - 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 10 wt%, from about 1 wt% to about 40 wt%, from about 1 wt% to about 35 wt%, from about 1 wt% to about 30 wt%, from about 1 wt% to about 25 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 10 wt%, from about 5 wt% to about 40 wt%, from about 5 5 wt% to about 35 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 25 wt%, or from about 5 wt% to about 20 wt%, or about 15 wt%, or about 17.5 (w/w)%. 21. The long-acting injectable formulation of any one of claims 1-20, wherein the amount of castor oil or a combination of castor oil and a second natural oil is from 40% (w/w) to about 10 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 75% (w/w), from 40% (w/w) to about 70% (w/w), from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). 15 22. The long-acting injectable formulation of claim 21 wherein the carrier comprises a combination of castor oil and a second natural oil. 23. The long-acting injectable formulation of claim 22, wherein the second natural oil is cottonseed oil. 20 24. The long-acting injectable formulation of any one of claims 1-20, wherein the long- acting formulation does contain not a second natural oil, and the amount of castor oil is from 40% (w/w) to about 90% (w/w), from 40% (w/w) to about 85% (w/w), from 40% (w/w) to about 80% (w/w), from 40% (w/w) to about 75% (w/w), from 40% (w/w) to about 70% (w/w), 25 from 40% (w/w) to about 65% (w/w), from 40% (w/w) to about 60% (w/w), or from 40% (w/w) to about 55% (w/w). 25. The long-acting injectable formulation of any one of claims 7-24, wherein the amount of the viscosity modifier ranges from about 0.01% to about 30%, from about 0.01% to about 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 145 - 20%, from about 0.1% to about 30%, from about 0.1% to about 20%, from about 0.1% to about 10%, from about 1% to about 30%, from about 1% to about 20%, from about 1% to about 10%, from about 5% to about 30%, from about 5% to about 20%, from about 10% to about 30%, from about 10% to about 20%, from about 0.01 to about 10%, from about 0.01 to 5 about 5%, or from about 0.05% to 1.0% (w/w). 26. The long-acting injectable formulation of any one of claims 7-25, wherein the amount of the emulsifier ranges from about 0.01% to about 50%, from about 0.01% to about 40%, from about 0.1% to about 50%, from about 0.1% to about 40%, from about 1% to about 50%, 10 from about 1% to about 40%, from about 10% to about 50%, from about 10% to about 40%, from about 20% to about 50%, from about 20% to about 45%, from about 0.01% to about 30%, from about 0.01% to about 20%, from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to 1.0% (w/w). 15 27. The long-acting injectable formulation of any one of claims 7-26, wherein the amount of the solubilizer ranges from about 0.01% to about 60% (w/w), from about 0.01 to about 50% (w/w), from about 0.01 to about 40% (w/w), from about 0.01 to about 30% (w/w), from about 1 to about 60% (w/w), from about 5 to about 60% (w/w), from about 10 to about 60% (w/w), from about 20 to about 60% (w/w), from about 30 to about 60% (w/w), from about 40 to about 20 60% (w/w), from about 15 to about 50% (w/w), from about 20 to about 50% (w/w), from about 15 to about 40% (w/w), from about 15 to about 35% (w/w), from about 15 to about 30% (w/w), from about 0.01 to about 10%, from about 0.01 to about 5%, or from about 0.05% to about 1.0% (w/w), or from about 15 to about 35% (w/w), about 20 to about 30% (w/w), or about 25% (w/w). 25 28. The long-acting injectable formulation of any one of claims 7-27, wherein the amount of the antioxidant ranges from about 0.01 to about 5%, from about 1 to about 5%, from about 2to about 5%, from about 3to about 5%, and from about 4to about 5%, from about 0.01% to about 3%, from about 0.01 to about 2%, or from about 0.05% to 1% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 146 - 29. The long-acting injectable formulation of any one of claims 7-28, wherein the amount of the preservative ranges from about 0.01 to about 10%, from about 0.01 to about 5%, from about 0.01 to about 1%, from about 0.1 to about 10%, from about 0.1 to about 5%, from about 5 0.1 to about 1%, from about 1% to about 10%, from about 1% to about 5%, from about 2% to about 10%, from about 2% to about 5%, from about 5 to about 10%, from about 0.01 to about 2%, or about 0.05 to about 1% (w/w). 30. The long-acting injectable formulation of any one of claims 1-6, wherein the carrier 10 further comprises: (a) from about from about 0.01% to about 20% (w/w), preferably from about 0.1% to 10% (w/w), of a viscosity modifier; and (b) one or more solubilizers and/or one or more emulsifiers, wherein the at least one parasiticidal isoxazoline active agent is dissolved in the 15 carrier, optionally, wherein the second natural oil is cotton seed oil, optionally, wherein the one or more solubilizers are present in an amount from about 0.01% to about 60% (w/w) or preferably, about 5% to about 30% (w/w) of the long-acting injectable formulation, 20 optionally, wherein the one or more solubilizers comprise glycerol formal, glycofurol, glycerol, or propylene carbonate, or a combination thereof, optionally, wherein the one or more emulsifiers are present in an amount from about 0.01% to about 50% (w/w) or preferably, from about 20% to 45%, (w/w) of the long-acting injectable formulation, and 25 optionally, wherein the one or more emulsifiers are selected from any one or more of the group consisting of propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, and polysorbate. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 147 - 31. The long-acting injectable formulation of claim 30, further comprising from about 0.01 to about 5.0% (w/w) of an antioxidant, preferably butylated hydroxyanisole. 5 32. The long-acting injectable formulation of any one of claims 30-31, wherein the viscosity modifier is ethyl oleate or ethanol, or a combination thereof. 33. The long-acting injectable formulation of any one of claims 30-32, wherein the solubilizer is glycerol formal or propylene carbonate, or a combination thereof. 10 34. The long-acting injectable formulation of any one of claims 30-33, wherein the emulsifier is propylene glycol monocaprylate or caprylocaproyl polyoxyl-8 glycerides, or a combination thereof. 15 35. The long-acting injectable formulation of any one of claims 1-6, wherein the at least one parasiticidal isoxazoline active agent is in the form of particles, and wherein the particles are suspended in the carrier, optionally, wherein the second natural oil is a glycerol triester of caprylic and capric acid, 20 wherein the carrier further comprises: (a) from about from about 0.01% to about 30% (w/w), preferably from about 5% to 30% (w/w) of a viscosity modifier; and (b) from about 0.01% to about 5% (w/w), preferably from about 0.1% to 1% (w/w) of an emulsifier. 25 36. The long-acting injectable formulation of claim 35, wherein the viscosity modifier is ethyl oleate. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 148 - 37. The long-acting injectable formulation of any one of claims 35-36, wherein the emulsifier is polysorbate 20. 5 38. A long-acting injectable formulation for the treatment and/or prevention of a parasitic infestation or infection in an animal comprising: i. at least one parasiticidal isoxazoline active agent, wherein the at least one parasiticidal active agent has a structure of (Ia) O ^N O F₃ 10 and ii. a carrier comprising castor oil, wherein the amount of castor oil in the formulation is at least 40% (w/w). 15 39. The long-acting injectable formulation of claim 38, wherein the at least one parasiticidal isoxazoline active agent has a structure of (S)-Ia: O F₃ , or a pharmaceutically acceptable salt thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 149 - 40. The long-acting injectable formulation of any one of claims 38-39, wherein the carrier further comprises polysorbate 20, Miglyol^® 812N, and ethyl oleate. 5 41. The long-acting injectable formulation of any one of claims 38-40, wherein the at least one parasiticidal isoxazoline active agent is in the form of particles, and wherein the particles are suspended in the carrier. 42. The long-acting injectable formulation of any one of claims 38-39, wherein the carrier 10 further comprises one or more excipients selected from the group consisting of ethanol, ethyl oleate, glycerol formal, propylene carbonate, Capryol^® 90, and Labrasol^®. 43. The long-acting injectable formulation of claim 42, wherein one or more excipients are selected from the group consisting of ethanol, ethyl oleate, and glycerol formal. 15 44. The long-acting injectable formulation of any one of claims 38-39, wherein the carrier further comprises two or three excipients selected from the group consisting of glycerol formal, ethanol and ethyl oleate. 20 45. The long-acting injectable formulation of any one of claims 1-44, wherein the formulation is at least 80% effective, at least 85% effective, or at least 90% effective at treating infestation by fleas and/or ticks for at least 6 months following a single administration to the animal. 25 46. The long-acting injectable formulation of any one of claims 1-45, further comprising a second active agent selected from the group consisting of an acaricide, an anthelmintic, an anti-parasitic, and an insecticide. 47. The long-acting injectable formulation of any one of claims 1-46, wherein long-acting 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 150 - indicates that the formulation provides at least 80%, preferably at least 85%, more preferably at least 90%, even more preferably at least 95%, most preferably more than 95% efficacy against ectoparasites, including but not limited to ticks and/or fleas, for at least 3 months, preferably at least 4 months, more preferably at least 5 months, even more preferably at least 5 6 months, most preferably more than 6 months. 48. The long-acting injectable formulation of claim 47 wherein the ectoparasites are fleas. 49. The long-acting injectable formulation of claim 47 wherein the ectoparasites are ticks. 10 50. A method for treating or preventing parasites in an animal comprising administering the long-acting injectable formulation of any one of claims 1-49 to the animal, preferably a non-human animal. 15 51. The method according to claim 50, wherein the long-acting injectable formulation is administered at one site or at more than one site of the animal in a single administration. 52. The method according to any one of claims 50-51, wherein the formulation is at least 80% effective, at least 85% effective, or at least 90% effective at treating or preventing 20 infestation by fleas and/or ticks for at least 6 months following a single administration to the animal, 53. The method of any one of claims 50-52, wherein the animal is a cat and/or a dog, especially a dog. 25 54. The method of any one or more of claims 50-53, wherein the long-acting injectable formulation is administered by subcutaneous injection. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 151 - 55. The method of any one of claims 50-54, wherein the dosage of the parasiticidal isoxazoline active agent administered to the animal is from about 0.1 to about 50 mg per kg of body weight, from about 0.5 to about 30 mg/kg, from about 0.5 to about 30 mg/kg body weight, from about 0.5 to about 20 mg/kg, from about 0.5 to about 10 mg/kg, from about 0.5 5 to about 5 mg/kg body weight, from about 0.5 to about 2.5 mg/kg body weight, from about 10 to about 30 mg/kg, from about 15 to about 30 mg/kg, or from about 20 to about 30 mg/kg of body weight of the animal. 56. The method of any one of claims 50-55, wherein the animal is a dog and wherein 10 following the administration, the site of injection has an injection site reaction (ISR) score of less than 2, as determined using the average diameter of a nodule formed at the site of injection. 57. A long-acting injectable formulation according to any one of claims 1-49 for use in 15 treating or preventing a parasitic infestation or infection in an animal, preferably a non-human animal, especially a cat and/or a dog. 58. The long-acting injectable formulation for use according to claim 57, wherein the parasitic infestation is a tick and/or a flea infestation. 20 59. Use of a long-acting injectable formulation according to any one of claims 1- 49 in the preparation of a medicament for treating or preventing a parasitic infestation or infection, preferably treating a parasitic infestation, in an animal, preferably a non-human animal, especially a cat and/or a dog. 25 60. Use of a compound according to any one of formulae I-VI: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 152 - wherein: A¹, A², A³, A⁴, A⁵ and A⁶ are independently selected from the group consisting of CR³ 5 and N, provided that at most 3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; B¹, B² and B³ are independently selected from the group consisting of CR² and N; W is O or S; R¹ is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents 10 independently selected from R⁶; each R² is independently H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or —NO₂; 15 each R³ is independently H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁- C6 alkylamino, C2-C6 dialkylamino, —CN or —NO2; R⁴ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 20 alkylcycloalkyl, C₄-C₇ cycloalkylalkyl, C₂-C₇ alkylcarbonyl or C₂-C₇ alkoxycarbonyl; R⁵ is H, OR¹⁰, NR¹¹R¹² or Q¹; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R⁴ and R⁵ are taken together with the nitrogen to which they are attached to form a ring 25 containing 2 to 6 atoms of carbon and optionally one additional atom selected from the group 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 153 - consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C1-C2 alkoxy; each R⁶ is independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 5 alkylsulfinyl, C₁-C₆ alkylsulfonyl, —CN or —NO₂; each R⁷ is independently halogen; C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3- C₆ cycloalkylamino, C₂-C₇ alkylcarbonyl, C₂-C₇ alkoxycarbonyl, C₂-C₇ alkylaminocarbonyl, C₃-C₉ dialkylaminocarbonyl, C₂-C₇ haloalkylcarbonyl, C₂-C₇ haloalkoxycarbonyl, C₂-C₇ 10 haloalkylaminocarbonyl, C3-C9 dihaloalkylaminocarbonyl, hydroxy, —NH2, —CN or —NO2; or Q²; each R⁸ is independently halogen, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁- C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C4 alkoxycarbonyl, —CN or — 15 NO₂; each R⁹ is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₁-C₆ alkylamino, C₂-C₆ dialkylamino, —CN, —NO₂, phenyl or pyridinyl; 20 R¹⁰ is H; or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one of more halogen; R¹¹ is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C2-C7 alkoxycarbonyl; 25 R¹² is H; Q³; or C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₄-C₇ alkylcycloalkyl or C4-C7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R⁷; or R¹¹ and R¹² are taken together with the nitrogen to which they are attached to form a ring containing 2 to 6 atoms of carbon and optionally one additional atom selected from the 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 154 - group consisting of N, S and O, said ring optionally substituted with 1 to 4 substituents independently selected from the group consisting of C₁-C₂ alkyl, halogen, —CN, —NO₂ and C1-C2 alkoxy; Q¹ is a phenyl ring, a 5- or 6-membered heterocyclic ring, or an 8-, 9- or 10-membered 5 fused bicyclic ring system optionally containing one to three heteroatoms selected from up to 1 O, up to 1 S and up to 3 N, each ring or ring system optionally substituted with one or more substituents independently selected from R⁸; each Q² is independently a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; 10 Q³ is a phenyl ring or a 5- or 6-membered heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from R⁹; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof; or R₁ A₁ N Y 15 wherein: R₁ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, 20 haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO2; X is aryl or heteroaryl, which may be unsubstituted or substituted by one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, 25 R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, R7C(O)NR8-, -CN or -NO2; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 155 - A1 is oxygen; and A₂ is oxygen, NR₂ or CR₇R₈; G is G-1 or G-2; B₃ B B₂ 5 B1, B2, B3, B4 a Y is hydrogen, halogen, -CN; or Y is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, aryl, or heterocyclyl or heteroaryl each of which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, 10 alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R₇S(O)-, R₇S(O)₂-, R₇C(O)-, R₇R₈NC(O)-, R₇OC(O)-, R₇C(O)O-, R₇C(O)NR₈-, -CN or -NO₂; or Y is Y-1, Y-2, Y-3, Y-4, Y-5, Y-6, Y-7, Y-8, Y-9, Y-10, Y-11, Y-12 or Y-13;

23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 156 - 1₃ ₄ , 4 hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, R10S(O)-, R10S(O)2-, R10C(O)-, R10C(S)-, R10R11NC(O)-, R10R11NC(S)- R10OC(O)-; 5 R₄, R₅ and R₆ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, aryl or heteroaryl; R₇ and R₈ are independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; 10 R9 is hydrogen, halogen, -CN, or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, halocycloalkyl, alkylcycloalkyl or cycloalkylalkyl, each which is unsubstituted or substituted with one or more of halogen, hydroxy, amino, alkyl- or di(alkyl)amino, alkyl, cycloalkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, R7S(O)-, R7S(O)2-, R7C(O)-, R7R8NC(O)-, R7OC(O)-, R7C(O)O-, 15 R₇C(O)NR₈-, -CN or -NO₂; R10, R11, R12 and R13 are each independently hydrogen, alkyl, haloalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl; or 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 157 - R10 together with R11 form =O, =S or =NR2; or R₁₂ together with R₁₃ form =O, =S or =NR₂; W is O, S or NR2; n is 1-4; and 5 m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; or O ^N O F₃C H CF₃ or a ph 10 or a p F₃C 1 O -T wherein R¹, R² an p y , , ; 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 158 - S Y is the diradical group _nd T is a C1-C6-alkyl grou or substituted by halogen, cyano, nitro, amino, hydroxyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-alkylthio, carboxy, carbamoyl or C₂-C₆-alkanoyl group which may be unsubstituted or substituted in the alkyl 5 portion by halogen or a pharmaceutical acceptable salt thereof; or OH Y B 3b wherein: Y is hydrogen, fluoro, chloro or bromo; 10 R¹ is phenyl substituted with 2-4 substituents selected from halogen, methyl, difluoromethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoroethoxy; R² is methyl, fluoromethyl, trifluoromethyl or perfluoroethyl; R^3a and R^3b are independently selected from hydrogen, methyl, ethyl or fluoromethyl; or R^3a and R^3b together combine with the carbon to which they are attached to form a 15 cyclopentyl ring or a cyclohexyl ring; or a pharmaceutically acceptable salt thereof; in the preparation of a medicament for use in treating or preventing infestation by fleas and/or ticks, wherein the medicament is in the form of a long-acting injectable formulation comprising a compound according to any one of formulae I-VI and a carrier comprising castor oil or a combination of castor oil and a second natural oil, wherein the amount of castor oil in the 20 formulation or the combination of castor oil and the second natural oil in the formulation is at least 40% (w/w). 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 159 - 61. A kit for preparing a composition for treating or preventing infestation by fleas and/or ticks according to claim 2, wherein the kit comprises a) an isoxazoline active agent having a structure of any one of formulae I-VI, or a 5 pharmaceutically acceptable salt thereof; b) a vehicle comprising a pharmaceutically acceptable excipient capable of forming a suspension or solution with said isoxazoline agent; and c) instructions for combining said isoxazoline active agent with the vehicle. 10 62. The kit of claim 61, wherein the parasiticidal isoxazoline active agent has a structure of I(a): F₃ , 15 63. The kit of claim 62, wherein the isoxazoline compound has a structure of (S)-Ia: O F₃ , or a pharmaceutically acceptable salt thereof. 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 160 - 64. A process for preparing a ready to use long-acting injectable formulation according to any one of claims 1-49 wherein the process comprises: a) providing at least one isoxazoline active agent; 5 b) providing a carrier comprising castor oil or a combination of castor oil and a second natural oil; c) combining the at least one isoxazoline active agent and the carrier in a container to provide a long-acting injectable formulation, and d) mixing the long-acting injectable formulation in the container for a period of time 10 according to instructions provided with the at least one isoxazoline agent. 65. The process according to claim 64, wherein said isoxazoline active agent is a compound that has a structure of I(a): O O F₃ , 15 , and wherein the amount of castor oil or combination of castor oil and a second natural oil in said formulation is at least 40% (w/w). 66. The process according to claim 65, wherein said isoxazoline active agent is a 20 compound that has a structure of (S)-Ia: 23-0052-WO-1 Boehringer Ingelheim Vetmedica GmbH - 161 - F3 , 5 10