WO2012058091A2 - Aripiprazole compositions and methods for its transdermal delivery - Google Patents

Aripiprazole compositions and methods for its transdermal delivery Download PDF

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Publication number
WO2012058091A2
WO2012058091A2 PCT/US2011/057080 US2011057080W WO2012058091A2 WO 2012058091 A2 WO2012058091 A2 WO 2012058091A2 US 2011057080 W US2011057080 W US 2011057080W WO 2012058091 A2 WO2012058091 A2 WO 2012058091A2
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Prior art keywords
pharmaceutical composition
composition
polymers
carbopol
arpz
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French (fr)
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WO2012058091A3 (en
Inventor
Fotios M. Plakogiannis
Muhammed Anwar Hossain
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ALPHA TO OMEGA PHARMACEUTICAL CONSULTANTS Inc
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ALPHA TO OMEGA PHARMACEUTICAL CONSULTANTS Inc
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Priority to AU2011320758A priority Critical patent/AU2011320758B2/en
Priority to CA2816203A priority patent/CA2816203C/en
Priority to RU2013124401/15A priority patent/RU2589689C2/en
Priority to BR112013010190A priority patent/BR112013010190B1/en
Priority to JP2013536677A priority patent/JP5966228B2/en
Priority to EP11836886.9A priority patent/EP2632463B1/en
Priority to ES11836886.9T priority patent/ES2675913T3/en
Priority to US13/879,485 priority patent/US9138402B2/en
Priority to CN201180052667.0A priority patent/CN103491961B/en
Priority to MX2013004693A priority patent/MX339196B/en
Application filed by ALPHA TO OMEGA PHARMACEUTICAL CONSULTANTS Inc filed Critical ALPHA TO OMEGA PHARMACEUTICAL CONSULTANTS Inc
Publication of WO2012058091A2 publication Critical patent/WO2012058091A2/en
Priority to US13/668,500 priority patent/US20130171237A1/en
Anticipated expiration legal-status Critical
Publication of WO2012058091A3 publication Critical patent/WO2012058091A3/en
Priority to US14/825,318 priority patent/US9757374B2/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the field of transdermal delivery of pharmaceutical compositions, which have an acceptable in vitro performance and good bioavailability.
  • the transdermal pharmaceutical compositions of the present invention include liquids or gels of aripiprazole in a patch dosage form.
  • ARPZ Aripiprazole
  • ARPZ is the first of a new class of atypical antipsychotics (third generation). Biochemically, ARPZ is a partial agonist of the D2 family of dopamine receptors. 1 ,2 It is active against positive and negative symptoms of schizophrenia. 3 ' 4 ARPZ is a quinolinone derivative, white crystalline powder, practically insoluble in water, with a low melting point (135-140°C), MW 448,38g/mole and partition coefficient of 4.54.
  • ARPZ is practically insoluble in water and has been formulated as a liquid and gel dosage form (Table 1 ). All reported values are in weight/volume percentage
  • the optimum composition of a 1 % W/V to 20% W/V ARPZ liquid formulation was predicted to have NMP 40%, DMSO 40%, Alcohol 15% and water 5% (Table 1 ).
  • the gel formulation should contain a gelling agent in the range of about 0.1 % to 5% W/V and the optimum APRZ composition should range from about 1 % W/V to 20% W/V with about .5% W/V of the gelling agent. Therefore, the gel formulation was predicted to have a NMP of 40%, DMSO 40%, Alcohol 15%, Carbopol 971 0.5%, and Water 4.5% (Table 1).
  • Table 2 lists other combinations that also could produce successful liquid and gel ARPZ formulations in accordance with the present invention.
  • NMP N-Methyl-2-Pyrolidone
  • DMSO Dimethl Sulfoxide
  • Ethyl Alcohol Ethyl Alcohol
  • solvents known to those skilled in the art suitable for use in the present invention can be used to prepare the liquid formulation, and combinations thereof, including but not limited to alcohols such as but not limited to (methyl, ethyl, butyl, propyl, isopropyl, isopropyl myristate, etc.), glycols such as, but not limited to(propylene, polyethylene, glycerin, etc.) mineral oils, vegetable oils, and others.
  • ARPZ can be gelled by gelling agents, including but not limited to, natural polymers (such as agar, alginic acid and derivatives, cassia tora, collagen, gelatin, gellum gum, guar gum, pectin, potassium, or sodium carageenan, tragacanth, xanthan, etc), semisynthetic polymers
  • ARPZ can be evaluated with other artificial membranes including but not limited to silicone membranes (polydimethylsiloxane), liposoem-coated membranes, solid-supported liquid membranes, lecithin organogel membranes and other.
  • other dosage forms including, but not limited to, ointments, creams, emulsions, liposomes, etc. may be used.
  • FIG. 1 Effect of Drug Concentration on the Flux of ARPZ through Cellulose Membrane from 0.5% Carbopol 971 Gel Systems
  • ARPZ gel formulation contained Why and Myristc acid.
  • enhancers including but not limited to water, sulfoxides, and similar chemicals, dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF),
  • decymethylsulfoxide etc, azone, pyrrolidones N-methyl-2-pyrrolidone (NMP), 2-pyrrolidon (2p), etc., fatty acids esters (butyl ethanoate, ethyl ethanoate, ethyl oleate, isopropyl myristate, isopropyl palmiate, methyl ethanoate etc), fatty acids (capric, caprylic, lauric, oleic, myristic, linoleic, stearic, palmitic etc), alcohols, fatty alcohols and glycols (nathanol, dodecanol, propylene glycols, glycerol etc), urea, essential oils, terpene and terpenoids (limonene, thymol, cineole etc), liposomes, niosomes, transferomes, ethanosomes etc.
  • NMP N-methyl-2-
  • Example 2 The effects of pH on the permeation of ARPZ through human cadaver skin were evaluated and a characteristic graph is shown in Figure 2.
  • the preferred optimum composition of ARPZ gel transdermal formulation had a pH in the range of approximately 6 to 7.
  • the ARPZ transdermal delivery may be influenced by pH values outside of the preferred range, but to a lesser extent.
  • the present invention may still be achieved outside of the preferred pH range of approximately 6 to7, depending upon the circumstances of use.
  • the systems of this discovery can deliver ARPZ at a flux between 50mcg/ch-2. h and 800mcg/ch-2.h, which can produce the required therapeutic ARPZ blood levels.
  • Flux rate can be changed by modifying such parameters as ARPZ initial concentration, surface area of the patch, pH of the formulation, vehicle composition, enhancer type and composition, etc., in accordance with the teachings of the present invention.
  • Optimum therapeutic outcome requires not only a proper drug selection but also an effective drug delivery.
  • Psychotropic drug compliance of rigorous regular medication schedules is of great importance.
  • oral administration of psychotropic agents is considered a less than optimal delivery system due to patient non-compliance 5 .
  • Transdermal delivery of psychotropic drugs, especially with prolonged duration of action, would be valuable in increasing medication compliance, especially in the geriatric population. Further, potential advantages of ARPZ transdermal delivery are as follows: lack of hepatic first pass effect;
  • Aripiprazole is a high affinity partial agonist at human D2 dopamine receptors. Int. J.Neuropsychopharmacol. 2000;3(Suppl. l), S 129.

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Abstract

The present invention discloses compositions of liquid and gel formulation containing aripiprazole in the form of a patch for transdermal delivery.

Description

ARIPIPRAZOLE COMPOSITIONS AND METHODS FOR ITS TRANSDERMAL DELIVERY
Field of the Invention
The present invention relates to the field of transdermal delivery of pharmaceutical compositions, which have an acceptable in vitro performance and good bioavailability. In particular, the transdermal pharmaceutical compositions of the present invention include liquids or gels of aripiprazole in a patch dosage form.
Background of Invention
Aripiprazole (ARPZ) is the first of a new class of atypical antipsychotics (third generation). Biochemically, ARPZ is a partial agonist of the D2 family of dopamine receptors.1 ,2 It is active against positive and negative symptoms of schizophrenia.3'4 ARPZ is a quinolinone derivative, white crystalline powder, practically insoluble in water, with a low melting point (135-140°C), MW 448,38g/mole and partition coefficient of 4.54.
Description of the Invention
Example
ARPZ is practically insoluble in water and has been formulated as a liquid and gel dosage form (Table 1 ). All reported values are in weight/volume percentage
(wyyj
TABLE 1: Composition of liquid and gel formulation of Aripiprazole (5% W/V)
Figure imgf000002_0001
An optimal mixture design of experiments was used to select the levels of the formulation variables. The optimum composition of a 1 % W/V to 20% W/V ARPZ liquid formulation was predicted to have NMP 40%, DMSO 40%, Alcohol 15% and water 5% (Table 1 ). The gel formulation should contain a gelling agent in the range of about 0.1 % to 5% W/V and the optimum APRZ composition should range from about 1 % W/V to 20% W/V with about .5% W/V of the gelling agent. Therefore, the gel formulation was predicted to have a NMP of 40%, DMSO 40%, Alcohol 15%, Carbopol 971 0.5%, and Water 4.5% (Table 1). However, Table 2 lists other combinations that also could produce successful liquid and gel ARPZ formulations in accordance with the present invention.
TABLE 2. Concentration Ranges of N-Methyl-2-Pyrolidone (NMP), Dimethl Sulfoxide (DMSO), Ethyl Alcohol, and Water in Liquid Aripiprazole
Formulation
Formulation NMP DMSO Alcohol Water
1. 50 50 —
2. 40 40 20 —
3. 40 40 — 20
4. 40 40 15 5
5. 40 40 10 10
6. 40 40 5 15
7. 30 30 20 20
8. 30 30 30 10
9. 30 40 25 5
10. 40 30 25 5
1 1. 45 45 10 0
12. 45 40 10 5 Other than these components, other solvents known to those skilled in the art suitable for use in the present invention can be used to prepare the liquid formulation, and combinations thereof, including but not limited to alcohols such as but not limited to (methyl, ethyl, butyl, propyl, isopropyl, isopropyl myristate, etc.), glycols such as, but not limited to(propylene, polyethylene, glycerin, etc.) mineral oils, vegetable oils, and others.
Example
The effect of gelling agents and their concentration on the permeation of ARPZ through artificial membranes and human cadaver skin was evaluated and two characteristic graphs are shown in Figures 1 & 2. The optimal desired composition of ARPZ gel formulation contains 0.5% W/V Carbopol 971. ARPZ can be gelled by gelling agents, including but not limited to, natural polymers (such as agar, alginic acid and derivatives, cassia tora, collagen, gelatin, gellum gum, guar gum, pectin, potassium, or sodium carageenan, tragacanth, xanthan, etc), semisynthetic polymers
(such as methylcellulose, carbosymethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, etc.) synthetic polymers (such as carboxyvinyl polymers or carbomers: carbopol 940, carbopol 934, carbopol 971 , poloxamer, polyacrylamide, polyvinyl alcohol, polyethylene, and its co-polymers etc), and clays (such as silicates, etc). In addition, other than cellulose membranes, ARPZ can be evaluated with other artificial membranes including but not limited to silicone membranes (polydimethylsiloxane), liposoem-coated membranes, solid-supported liquid membranes, lecithin organogel membranes and other. Besides the gel formulations of ARPZ, other dosage forms including, but not limited to, ointments, creams, emulsions, liposomes, etc. may be used.
Figure 1: Effect of Drug Concentration on the Flux of ARPZ through Cellulose Membrane from 0.5% Carbopol 971 Gel Systems
Figure imgf000004_0001
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00
Drug (ARPZ) Concentration (%) Figure 2: Cumulative Amount of 5% ARPZ Permeated through Cadaver Skin from 0.5% Carbopol Gel System
Cumulative Amount of Drug Permeated through
Cadaver Skin from 5% ARPZ in 0.5% Carbopol Gel Systems
Figure imgf000005_0001
0 5 1 0 15 20 25 30 35 40 45 50 55 60 65 70
Time (Hours)
Example
The effect of enhancers on the flux of ARPZ through human cadaver skin was evaluated and is shown in Figure 3. The desired optimum composition of ARPZ gel formulation contained Laurie and Myristc acid. Apart from Laurie and Myristc acid enhancer, the ARPZ transdermal delivery can be influenced by enhancers including but not limited to water, sulfoxides, and similar chemicals, dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), dimethylformamide (DMF),
decymethylsulfoxide (DCMS) etc, azone, pyrrolidones N-methyl-2-pyrrolidone (NMP), 2-pyrrolidon (2p), etc., fatty acids esters (butyl ethanoate, ethyl ethanoate, ethyl oleate, isopropyl myristate, isopropyl palmiate, methyl ethanoate etc), fatty acids (capric, caprylic, lauric, oleic, myristic, linoleic, stearic, palmitic etc), alcohols, fatty alcohols and glycols (nathanol, dodecanol, propylene glycols, glycerol etc), urea, essential oils, terpene and terpenoids (limonene, thymol, cineole etc), liposomes, niosomes, transferomes, ethanosomes etc.
Figure 3. Cumulative Amount of Drug Permeated through Human Cadaver
Skin from 5% ARPZ in 0.5% Carbopol Gel Systems with Enhancers (Fatty Acids) Cumulative Amount of Drug Permeated through Human Cadaver Skin from 5% ARPZ in 0.5% Carbopol Gel Systems with Enhancers (Fatty Acids)
Figure imgf000006_0001
Time (Hours)
Example The effects of pH on the permeation of ARPZ through human cadaver skin were evaluated and a characteristic graph is shown in Figure 2. The preferred optimum composition of ARPZ gel transdermal formulation had a pH in the range of approximately 6 to 7. Other than these optimal pH values, the ARPZ transdermal delivery may be influenced by pH values outside of the preferred range, but to a lesser extent. Thus, the present invention may still be achieved outside of the preferred pH range of approximately 6 to7, depending upon the circumstances of use.
The systems of this discovery can deliver ARPZ at a flux between 50mcg/ch-2. h and 800mcg/ch-2.h, which can produce the required therapeutic ARPZ blood levels. Flux rate can be changed by modifying such parameters as ARPZ initial concentration, surface area of the patch, pH of the formulation, vehicle composition, enhancer type and composition, etc., in accordance with the teachings of the present invention.
Optimum therapeutic outcome requires not only a proper drug selection but also an effective drug delivery. Psychotropic drug compliance of rigorous regular medication schedules is of great importance. In many instances, oral administration of psychotropic agents is considered a less than optimal delivery system due to patient non-compliance5. Transdermal delivery of psychotropic drugs, especially with prolonged duration of action, would be valuable in increasing medication compliance, especially in the geriatric population. Further, potential advantages of ARPZ transdermal delivery are as follows: lack of hepatic first pass effect;
eliminating the potential for over- or under- dosing; allowing the flexibility of terminating the drug administration by simply removing the patch; providing a simplified therapeutic regimen, thereby assisting medication compliance in the geriatric population.
References
1. Inoue,T., Domae,M.,Yamada,K.,and Furukawa,T. Effects of the novel antipsychotic agent 7-( [4-2,3-dichlorophenylo-l-piperazinyl ] b Neuroutyloxyo-3,4- dihydro2 (1H ) -quinolinone ( OPC- 14597) on prolactin release from the rat anterior pituitary. J.Pharmacol. Exp. Ther. 1996;277(1): 137-143.
2. Burris,K.D., Moiski/T.F., Ryan,E., Xu,C, Tottori,K., Kikuchi,T., Yocca,F.D, and Molinoff,P.B. Aripiprazole is a high affinity partial agonist at human D2 dopamine receptors. Int. J.Neuropsychopharmacol. 2000;3(Suppl. l), S 129.
3.Petrie,J.L., Saha,A.R., and McEvoyJ.P. Aripiprazole, a new atypical
antipsychotic: Phase II clinical trial results. Eur.Neuropsychopharm 1997; 7 (Suppl 2): S227.
4. Saha,A.R., McQuade,R., Carson,W.H.,Ali,M.,W.,Durbar,G.C.,and Ingenito,G. Efficacy and safety of Aripiprazole and Risperidone vs.Placebo in patients with schizophrenia and schizoaffective disorder. World J. Biol Psych 2001 ; 2 ( Suppl 1 ):
305S.
5. Geeta,A., Sanju, D., Psychotropic Drugs and Transdermal Delivery. An
Overview. Int. J. of Pharma and Bio Science, 2001 ;V 1(2).

Claims

Claims
1. A pharmaceutical composition comprising aripiprazole in a dosage form for transdermal delivery.
2. The pharmaceutical composition of claim 1 wherein the aripirazole is in a gel or liquid form.
3. The pharmaceutical composition of claim 1 wherein the aripirazole is present in the amount of 1 to 20% w/v.
4. The pharmaceutical composition of claim 2 wherein the aripirazole is present in the amount of 1 to 20% w/v.
5. The pharmaceutical composition of claim 2 wherein the gel contains a gelling agent in the range of about 0.1% to 5% w/v.
6. The pharmaceutical composition of claim 1 further comprising
approximately 40% N-methyl-2-pyrrolidone, 40% DiMethylsulfoxide, 15% alcohol and 5% water.
7. The pharmaceutical composition of claim 1 being in the form of a liquid and comprising an alcohol, glycol, mineral oil, and/or vegetable oil.
8. The pharmaceutical composition of claim 2 wherein the composition is in a gel form and further comprises a gelling agent selected from the group consisting of natural polymers, semisynthetic polymers, synthetic polymers, carboxyvinyl polymers or carbomers, carbopol 940, carbopol 934, carbopol 971 , poloxamer, polyacrylamide, polyvinyl alcohol, polyethylene and co-polymers thereof.
9. The pharmaceutical composition of claim 1 wherein the form is a patch for transdermal delivery.
10. The pharmaceutical composition of claim 1 being in the dosage form of an ointment, cream, emulsion, or liposome.
11. The pharmaceutical composition of claim 10 wherein the aripirazole is present in the amount of 1 to 20% w/v.
12. The pharmaceutical composition of claim 1 further comprising an enhancer.
13. The pharmaceutical composition of claim 12 wherein the enhancer is selected from the group consisting of lauric acid, myristc acid, water, sulfoxides, dimethylsulfoxide, dimethylacetamide, dimethylformamide, decymethylsulfoxide, azone, pyrrolidones, fatty acid esters, fatty acids, alcohols, fatty alcohols and glycols, urea, essential oilds, terpene and terpenoids, liposomes, niosomes, transferomes and ethanosomes.
14. The pharmaceutical composition of claim 1 wherein the pH of the composition is approximately 6 to 7.
15. The pharmaceutical composition of claim 4 wherein the pH of the composition is approximately 6 to 7.
PCT/US2011/057080 2010-10-28 2011-10-20 Aripiprazole compositions and methods for its transdermal delivery Ceased WO2012058091A2 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
CN201180052667.0A CN103491961B (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for transdermal administration thereof
RU2013124401/15A RU2589689C2 (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for transdermal delivery
BR112013010190A BR112013010190B1 (en) 2010-10-28 2011-10-20 pharmaceutical composition
JP2013536677A JP5966228B2 (en) 2010-10-28 2011-10-20 Aripiprazole composition
EP11836886.9A EP2632463B1 (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for their transdermal delivery
ES11836886.9T ES2675913T3 (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for transdermal administration
US13/879,485 US9138402B2 (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for its transdermal delivery
AU2011320758A AU2011320758B2 (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for its transdermal delivery
CA2816203A CA2816203C (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for its transdermal delivery
MX2013004693A MX339196B (en) 2010-10-28 2011-10-20 Aripiprazole compositions and methods for its transdermal delivery.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160354369A1 (en) * 2015-06-08 2016-12-08 Corium International, Inc. Formulations for aripiprazole delivery transdermally
EP3233077A1 (en) 2014-12-19 2017-10-25 The Broad Institute Inc. Dopamine d2 receptor ligands
WO2017188260A1 (en) * 2016-04-25 2017-11-02 Otsuka Pharmaceutical Co., Ltd. Compositions of pharmaceutical product with ingestible event marker

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9757374B2 (en) 2010-10-28 2017-09-12 Aequus Pharmaceuticals Inc. Aripiprazole compositions and methods for its transdermal delivery
WO2014172344A1 (en) * 2013-04-16 2014-10-23 Alpha To Omega Pharmaceutical Consultants, Inc. Pharmaceutical compositions
US10356018B2 (en) 2014-01-31 2019-07-16 Vivint, Inc. User management methods and systems
WO2017025912A1 (en) * 2015-08-13 2017-02-16 Aequus Pharmaceuticals Inc. Aripiprazole compositions and methods for its transdermal delivery
EP3441068A4 (en) * 2016-05-12 2019-04-10 FUJIFILM Corporation Transdermal preparation
WO2018117125A1 (en) * 2016-12-19 2018-06-28 富士フイルム株式会社 Transdermal preparation
WO2024226871A1 (en) * 2023-04-27 2024-10-31 Mccord Darlene E Compositions and methods of dissolving biofilm to promote wound healing

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040170672A1 (en) 2001-03-07 2004-09-02 Thorsten Selzer Transdermal therapeutic system for administration of partial dopamine-d2 agonists
WO2007035348A2 (en) 2005-09-15 2007-03-29 Elan Pharma International, Limited Nanoparticulate aripiprazole formulations

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL101492A0 (en) 1992-04-03 1992-12-30 Shalom Levy Anti-skin rash preparation
US5616602A (en) * 1993-07-09 1997-04-01 Ciba-Geigy Corporation Topically administrable zinc phthalocyanine compositions
HUT72887A (en) * 1994-02-18 1996-06-28 Drossapharm Ag Transdermal composition with controlled release
US5558071A (en) * 1994-03-07 1996-09-24 Combustion Electromagnetics, Inc. Ignition system power converter and controller
IL134830A0 (en) * 2000-03-01 2001-05-20 Chay 13 Medical Res Group N V Peptides and immunostimulatory and anti-bacterial pharmaceutical compositions containing them
DE10030716A1 (en) * 2000-06-23 2002-01-03 Degussa Low temperature impact resistant polymer alloy
DE10110953A1 (en) * 2001-03-07 2002-09-19 Lohmann Therapie Syst Lts Transdermal therapeutic system for the administration of partial dopamine D2 agonists
CA2428237C (en) * 2003-05-08 2010-07-20 Delmar Chemicals Inc. Process for the preparation of carbostyril derivatives
BRPI0415531B8 (en) * 2003-10-23 2021-05-25 Otsuka Pharma Co Ltd formulation of sterile injectable controlled-release aripiprazole and method for its preparation
PT1613598E (en) * 2003-12-16 2012-01-13 Teva Pharma Methods of preparing aripiprazole crystalline forms
MX339603B (en) * 2006-09-25 2016-05-31 Archer-Daniels-Midland Company Superabsorbent surface-treated carboxyalkylated polysaccharides and process for producing same.
US20100098735A1 (en) * 2006-10-05 2010-04-22 Rajesh Jain Injectable depot compositions and its process of preparation
US20130084243A1 (en) * 2010-01-27 2013-04-04 Liliane Goetsch Igf-1r specific antibodies useful in the detection and diagnosis of cellular proliferative disorders
WO2009060473A2 (en) * 2007-11-06 2009-05-14 Panacea Biotec Limited Injectable compositions, processes and uses thereof
CN104224703A (en) * 2008-09-25 2014-12-24 赛福伦公司 Liquid Formulations Of Bendamustine
GB0905365D0 (en) * 2009-03-27 2009-05-13 Norbrook Lab Ltd A topical parasiticide composition
EP2238976B1 (en) * 2009-04-03 2012-06-27 Hexal AG Oral films comprising 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro- 1H-quinolin-2-one base or salts or hydrates thereof
US8815261B2 (en) * 2009-06-19 2014-08-26 Medrx Co., Ltd. Composition for external application comprising aripiprazole and organic acid as active ingredients
US20110028412A1 (en) * 2009-08-03 2011-02-03 Cappellos, Inc. Herbal enhanced analgesic formulations
US9358261B2 (en) * 2011-10-25 2016-06-07 U.S. Phytotherapy, Inc. Additional artemisinin and berberine compositions and methods of making
US9968740B2 (en) * 2014-03-25 2018-05-15 Surefire Medical, Inc. Closed tip dynamic microvalve protection device
AR103332A1 (en) * 2014-12-31 2017-05-03 Valent Usa Corp DIGLICOLAMINE DICAMBA AND LACTOFEN LIQUID FORMULATIONS

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040170672A1 (en) 2001-03-07 2004-09-02 Thorsten Selzer Transdermal therapeutic system for administration of partial dopamine-d2 agonists
WO2007035348A2 (en) 2005-09-15 2007-03-29 Elan Pharma International, Limited Nanoparticulate aripiprazole formulations

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BURRIS,K.D.; MOISKI,T.F.; RYAN,E.; XU,C.; TOTTORI,K.; KIKUCHI,T.; YOCCA,F.D; MOLINOFF,P.B.: "Aripiprazole is a high affinity partial agonist at human D2 dopamine receptors", INT. J.NEUROPSYCHOPHARMACOL., vol. 3, no. L, 2000, pages S129
GEETA,A.; SANJU, D.: "Psychotropic Drugs and Transdermal Delivery. An Overview", INT. J. OF PHARMA AND BIO SCIENCE, vol. 1, no. 2, 2001
INOUE,T.; DOMAE,M.; YAMADA,K.; FURUKAWA,T.: "Effects of the novel antipsychotic agent 7-( [4-2,3-dichlorophenylo-l-piperazinyl ] b Neuroutyloxyo-3,4-dihydro2 (1H ) -quinolinone ( OPC-14597) on prolactin release from the rat anterior pituitary", J.PHARMACOL. EXP. THER, vol. 277, no. 1, 1996, pages 137 - 143
PETRIE,J.L.; SAHA,A.R.; MCEVOY,J.P.: "Aripiprazole, a new atypical antipsychotic: Phase II clinical trial results", EUR.NEUROPSYCHOPHARM, vol. 7, no. 2, 1997, pages S227
SAHA,A.R.; MCQUADE,R.; CARSON,W.H.; ALI,M.,W.; DURBAR,G.C.; INGENITO,G.: "Efficacy and safety of Aripiprazole and Risperidone vs.Placebo in patients with schizophrenia and schizoaffective disorder", WORLD J. BIOL PSYCH, vol. 2, no. 1, 2001, pages 305S
See also references of EP2632463A4

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3233077A1 (en) 2014-12-19 2017-10-25 The Broad Institute Inc. Dopamine d2 receptor ligands
US20160354369A1 (en) * 2015-06-08 2016-12-08 Corium International, Inc. Formulations for aripiprazole delivery transdermally
US9913840B2 (en) * 2015-06-08 2018-03-13 Corium International, Inc. Formulations for aripiprazole delivery transdermally
WO2017188260A1 (en) * 2016-04-25 2017-11-02 Otsuka Pharmaceutical Co., Ltd. Compositions of pharmaceutical product with ingestible event marker

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