WO2023173182A1 - Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation - Google Patents

Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation Download PDF

Info

Publication number
WO2023173182A1
WO2023173182A1 PCT/BR2022/050092 BR2022050092W WO2023173182A1 WO 2023173182 A1 WO2023173182 A1 WO 2023173182A1 BR 2022050092 W BR2022050092 W BR 2022050092W WO 2023173182 A1 WO2023173182 A1 WO 2023173182A1
Authority
WO
WIPO (PCT)
Prior art keywords
vilazodone
docusate
salt
add
pharmaceutical composition
Prior art date
Application number
PCT/BR2022/050092
Other languages
English (en)
Portuguese (pt)
Inventor
Carolina FALASCHI SAPONI
Luiz Felipe DE OLIVEIRA FARIA
Rossana BARCELLOS FRIEDRICH
Original Assignee
Eurofarma Laboratórios S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eurofarma Laboratórios S.A. filed Critical Eurofarma Laboratórios S.A.
Priority to PCT/BR2022/050092 priority Critical patent/WO2023173182A1/fr
Publication of WO2023173182A1 publication Critical patent/WO2023173182A1/fr

Links

Classifications

    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Definitions

  • the present invention relates to a vilazodone salt, specifically, vilazodone docusate, the process for obtaining said salt and a pharmaceutical composition comprising vilazodone docusate.
  • the present invention also relates to the use of the vilazodone docusate salt and the use of the composition comprising the respective salt.
  • Polymorphic forms or different salts of a given substance may have different chemical and physical properties, such as melting point, chemical reactivity, toxicity, solubility, dissolution rate, rheological properties and density. These characteristics can directly affect the processability and manufacturing of the active pharmaceutical ingredient (IFA) and the pharmaceutical form that contains it, as well as stability, dissolution, absorption in the gastrointestinal tract, bioavailability and organoleptic properties. Thus, the polymorphic form or type of salt of an active pharmaceutical ingredient (IFA) can impact the quality, safety and efficacy of a pharmaceutical product.
  • hydrochloride salt of vilazodone are further described in patent applications US9145400, US20140303185, WO201 4049612, US9505744 and US1001 1590.
  • Other salts of the active vilazodone with anions other than the hydrochloride are disclosed in documents WO201 4028473 and W O2014049609, the salts being claimed formed from the reaction of the base form of vilazodone with the following acids: phosphoric acid, sulfuric acid, methanesulfonic acid, lactic acid, maleic acid, benzoic acid, hydrobromic acid, oxalic acid, benzenesulfonic acid, para-toluenesulfonic acid, succinic acid, salicylic acid, tartaric acid, fumaric acid, malonic acid, pivalic acid, ascorbic acid and citric acid.
  • Hydrochlorides are the most common salts for weak bases, but their widespread use is not only due to convenience, as they are derived from a very strong acid (hydrochloric acid - HCI), favoring the formation of salt, but also because the Chloride ions (Cl ) are part of the group of most abundant electrolytes in the human body and, therefore, are expected not to cause physiological changes in the body.
  • hydrochlorides have low molecular weight and low toxicity, they present a decrease in solubility and dissolution rate in solutions with an excess of ions of the same type. This phenomenon is explained based on the law of mass action, for example, in a dissolution medium in HCI, and is known as the “common ion effect”.
  • Another important point when choosing a new salt refers to the occurrence of polymorphism.
  • an ideal drug must maintain its physical properties for long periods of storage so that repeated observations generate the same characteristics, such as melting point or solubility.
  • many salts are polymorphic, that is, they are capable of existing in two or more crystalline forms with different arrangements and/or conformations of molecules and, in addition, they can transform from one form to another in the solid state.
  • Polymorphism is a phenomenon that can be observed in more than half of APIs, and can be problematic, especially if one form transforms into another with different physical properties during the production of the drug. This can generate final substances with unpredictable characteristics.
  • Vilazodone hydrochloride has low solubility, being a class II API (slightly soluble and very permeable) in the Biopharmaceutical Classification System. Furthermore, vilazodone hydrochloride salt presents many polymorphic crystalline forms (more than a dozen, including anhydrous, hydrate and solvate forms) and amorphous forms.
  • Patent applications WO2014199313 and WO201 3175361 describe a process for obtaining vilazodone hydrochloride.
  • Patent document WO2013164794 describes crystalline forms A, B and C of vilazodone hydrochloride.
  • Patent document EP3360543 describes a pharmaceutical composition
  • a pharmaceutical composition comprising vilazodone hydrochloride, crospovidone, lactose monohydrate, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and coating, wherein said composition can be incorporated in solid pharmaceutical form, as in a coated tablet, a multilayer tablet, an orally disintegrating tablet, an immediate release tablet, a pill, a capsule, among others.
  • FIG. 1 shows the characteristic X-ray diffractogram of vilazodone docusate obtained by synthesis routes (A) and (B).
  • Figure 2 shows the X-ray diffractograms of vilazodone docusate (A), vilazodone hydrochloride (B) and sodium docusate (C).
  • Figure 3 shows the characteristic infrared absorption spectra of vilazodone docusate (A), sodium docusate (B) and vilazodone hydrochloride (C).
  • FIG 4 shows the analysis curves thermogravimetric measurement (TGA) obtained with a heating rate of 10 °C/min for vilazodone docusate (A) and vilazodone hydrochloride (B).
  • DSC differential scanning calorimetry
  • FIG. 6 shows the infrared absorption spectra for vilazodone docusate after synthesis (A), after incubation at 50 °C and 75% RH for 10 days (B) and stored at ambient conditions for 3 months (C) .
  • FIG. 7 shows the X-ray diffractograms for vilazodone docusate after synthesis (A), after incubation at 50 °C and 75% RH for 10 days (B) and stored at ambient conditions for 3 months (C) .
  • the present invention relates to a new vilazodone salt, its obtaining process and a pharmaceutical composition comprising it.
  • vilazodone salt commercially available in the form of vilazodone hydrochloride
  • the present invention reveals the synthesis of a new salt of this active ingredient, vilazodone docusate with improved solubility in a simulated gastric environment, absence of polymorphism, and its potential use in pharmaceutical compositions.
  • the compound has greater solubility in hydrochloric acid solutions, due to the absence of the effect of the common ion, and no polymorphs of the new salt were found under the conditions investigated. These characteristics can enable the use of a raw material without the risk of contamination with other polymorphic forms and, mainly, the development of new pharmaceutical forms with improved bioavailability of the active pharmaceutical ingredient.
  • the present invention presents as its first object, the vilazodone docusate salt.
  • the present invention presents a process for obtaining vilazodone docusate, as described in the first object and in any of its embodiments, comprising the steps of:
  • the present invention presents a process for obtaining vilazodone docusate, as described in the first object and in any of its embodiments, comprising the steps of:
  • the present invention presents a pharmaceutical composition
  • a pharmaceutical composition comprising (a) vilazodone docusate, as described in the first object and in any of its embodiments; and (b) one or more pharmaceutically acceptable excipients.
  • the present invention presents the use of vilazodone salt, as described in the first object and in any of its embodiments, for the preparation of a medicine for the treatment of major depressive disorder (MDD).
  • MDD major depressive disorder
  • the vilazodone docusate salt of the present invention may have fewer impurities, desirable pharmacokinetic properties for immediate and modified release formulations and ease of pharmaceutical processing.
  • the expression “peaks expressed in 2-theta degrees” refers to the characteristic peaks of the diffractogram X-ray obtained using a wavelength of 1.54 ⁇ (Cu K-alpha) of vilazodone docusate salt.
  • the present invention relates to obtaining and using the salt of vilazodone docusate or 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate of 5-(4-[4-(5-cyano- 17 J-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide, with molecular formula C46H64N5O9S and molecular mass 862 g/mol, for use in pharmaceutical preparations and compositions.
  • the present invention presents the vilazodone docusate salt.
  • the vilazodone docusate salt presents peaks expressed in degrees 2-theta ( ⁇ 0.2°) to 3.8; 7.5; 1 1 .3; 12.9; 15.2; 18.0; 19.0; 21.6; 22.7; 23.9 and 28.0 on its X-ray diffractogram.
  • the vilazodone docusate salt presents specific peaks expressed in degrees 2-theta ( ⁇ 0.2°) to 3.8; 7.5 and 15.2 on your X-ray diffractogram.
  • the vilazodone docusate salt presents characteristic bands 3477; 2976; 2926; 2860; 2219; 1735; 1680; 1601; 1022; 961; 940; 888; 853; 810; 761 cm' 1 in its absorption spectrum in the infrared region.
  • the salt has a melting point in the range of 172 to 178°C.
  • the present invention presents a process for obtaining vilazodone docusate, as described in the first object and in any of its embodiments, comprising the steps of:
  • the process comprises the steps of:
  • the process comprises the steps of: (i) Add 60 mg of docusate sodium to 200 mL of water in a beaker and stir until complete solubilization;
  • the present invention presents a process for obtaining vilazodone docusate, as described in the first object and in any of its embodiments, comprising the steps of:
  • the process comprises the steps of:
  • the process comprises the steps of:
  • the present invention presents a pharmaceutical composition
  • a pharmaceutical composition comprising (a) vilazodone docusate, as defined in the first object and in any of its embodiments; and (b) one or more pharmaceutically acceptable excipients.
  • the excipients in (b) comprise one or more pharmaceutically acceptable excipients selected from diluents, disintegrants, glidants, lubricants, coloring agents, opacifiers and, optionally, coatings.
  • the excipients in (b) comprise one or more pharmaceutically acceptable excipients selected from the group consisting of lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide and vegetable magnesium stearate.
  • the excipients of the composition can be used in other ranges of values (in % by mass) or replaced by excipients with the same function in the formulation.
  • lactose is present in the composition of the present invention in the range of 0 to 80%; material with a diluent function, which can be combined or totally replaced by one or more excipients, combined or not, including but not limited to: microcrystalline cellulose, dibasic calcium phosphate, tribasic calcium phosphate, mannitol, starch, pregelatinized starch , sucrose, erythritol, xylitol, maltitol, glucose, dextrose, kaolin, calcium sulfate and talc in a proportion of 10 to 80% w/w of the composition.
  • material with a diluent function which can be combined or totally replaced by one or more excipients, combined or not, including but not limited to: microcrystalline cellulose, dibasic calcium phosphate, tribasic calcium phosphate, mannitol, starch, pregelatinized starch , sucrose, erythritol, xylitol,
  • microcrystalline cellulose is present in the composition of the present invention in the range of 0 to 80%; material with a diluent function, which can be combined or completely replaced by one or more excipients, combined or not, including but not limited to: lactose, dibasic calcium phosphate, tribasic calcium phosphate, mannitol, starch, pregelatinized starch, kaolin, sucrose, erythritol, xylitol, maltitol, glucose, dextrose, calcium sulfate and talc in a ratio of 10 to 80% w/w of the composition.
  • material with a diluent function which can be combined or completely replaced by one or more excipients, combined or not, including but not limited to: lactose, dibasic calcium phosphate, tribasic calcium phosphate, mannitol, starch, pregelatinized starch, kaolin, sucrose, erythritol, xylito
  • croscarmellose sodium is present in the composition of the present invention in the range of 0 to 5%; usual limit range of this specific excipient.
  • This material acts as a disintegrant and can be exempt from the formulation, combined or completely replaced by one or more excipients, combined or not, in a proportion of 2 to 30% w/w of the formulation, including but not limited to: sodium starch glycolate, magnesium and aluminum silicate, magnesium and aluminum silicate, starch, pregelatinized starch, pectins, alginates, microcrystalline cellulose, alginic acid, alpha cellulose, potassium polacrilin, calcium carboxymethylcellulose, sodium carboxymethylcellulose.
  • colloidal silicon dioxide is found in the composition of the present invention in the range of 0.05 to 2%; material with a sliding function, which may be exempt from the formulation, combined or replaced by one or more excipients, combined or not with each other, in a proportion of 0.05 to 10% w/w of the formulation, including, but not limited to, talc, magnesium oxide, magnesium trisilicate and cellulose.
  • magnesium stearate is present in the composition of the present invention in the range of 0.2 to 5%; material with a lubricant function, which may be exempt from the formulation, combined or replaced by one or more excipients, combined or not, in a proportion of 0.2 to 10% w/w of the formulation, including but not limited to talc, calcium stearate, sodium lauryl sulfate, castor oil, sodium benzoate, hydrogenated vegetable oil, sodium stearyl fumarate, magnesium lauryl sulfate, stearic acid, calcium stearate, glyceryl behenate, glyceryl monostearate, polyethylene glycols, polysorbates and zinc stearate.
  • composition pharmaceutical has the following composition:
  • Disintegrant from 2 to 30%;
  • Lubricant from 0.2 to 10%.
  • the pharmaceutical composition has the following composition:
  • Lactose monohydrate from 0 to 80%
  • Microcrystalline cellulose from 0 to 80%;
  • Vegetable magnesium stearate from 0.2 to 5%.
  • the pharmaceutical composition has the following composition:
  • the composition additionally comprises coating in the range of 1 - 5% weight gain.
  • the use of coating on tablets is optional in the recommended range of 1 - 5% weight gain, and ready-made coating systems can be used, such as Opadry®, or proceed with the formation of based films, but not limited to polymers polyvinyl alcohol (PVA) and hydroxypropylmethylcellulose (HMPC), plasticizing agents such as polyethylene glycol (PEG) and triethylcitrate, opacifiers such as titanium dioxide and colorants such as lacquers and iron oxides.
  • PVA polyvinyl alcohol
  • HMPC hydroxypropylmethylcellulose
  • plasticizing agents such as polyethylene glycol (PEG) and triethylcitrate
  • opacifiers such as titanium dioxide
  • colorants such as lacquers and iron oxides.
  • the present invention presents the use of vilazodone salt, as described in the first object and in any of its embodiments, for the preparation of a medicine for the treatment of major depressive disorder (MDD).
  • MDD major depressive disorder
  • vilazodone salt is also used for the preparation of a medicine for the treatment and prevention of anxiety disorders, bipolarity, mania, dementia, substance-related disorders, sexual dysfunctions, eating disorders, obesity, fibromyalgia, sleep disorders, psychiatric disorders, cerebral infarction, tension, for the therapy of side effects in the treatment of hypertension, cerebral disorders, chronic pain, acromegaly, hypogonadism, secondary amenorrhea, premenstrual syndrome and unwanted puerperal lactation.
  • the new vilazodone docusate salt may include advantages such as fewer impurities, desirable pharmacokinetic properties for immediate and modified release formulations and ease of pharmaceutical processing.
  • the new vilazodone salt based on the counterion Docusate can be an alternative to vilazodone hydrochloride in the production of innovative, safe and effective pharmaceutical forms.
  • Obtaining an active pharmaceutical ingredient with improved solubility characteristics, adequate stability and not susceptible to polymorphism opens up possibilities for developing innovative pharmaceutical forms for an already consolidated therapy, such as solutions, soft capsules and hard capsules.
  • Example 1 Synthesis methodology - Reaction of vilazodone hydrochloride with sodium docusate in aqueous medium followed by extraction with apolar solvent (A).
  • Example 2 Reaction of vilazodone hydrochloride with sodium docusate in DMSO solvent followed by the addition of water with precipitation of the vilazodone docusate salt (B).
  • DMSO dimethyl sulfoxide
  • B precipitation of the vilazodone docusate salt
  • Figure 1 presents the characteristic X-ray diffractogram for the vilazodone docusate salt obtained by synthesis routes (A) and (B) and Table 1 contains the angles and relative intensity of the main peaks in the salt diffractogram.
  • Figure 2 the X-ray diffractogram for the vilazodone docusate salt (A) is shown together with the diffractograms of the vilazodone hydrochloride (B) and sodium docusate (C) salts, used as starting reagents, illustrating the difference in position of diffraction peaks for different crystalline forms.
  • Figure 4 shows the thermogravimetric analysis (TGA) that indicates a residual moisture of 0.2% by mass of vilazodone docusate (isotherm at 105 ° C for 60 minutes) (A) and a decomposition temperature of approximately 260 °C, a value similar to that found for vilazodone hydrochloride (B).
  • TGA thermogravimetric analysis
  • DSC Differential Scanning Calorimetry
  • Table 2 shows the composition of vilazodone docusate tablets, containing excipients commonly used in the pharmaceutical industry.
  • Table 2 Quali-quantitative composition of vilazodone docusate tablets.
  • vilazodone docusate is equivalent to 0.498 mg of vilazodone in free base form.
  • the dosage is relative to the hydrochloride salt, with 1.00 mg of vilazodone hydrochloride equivalent to 0.92 mg of vilazodone in free base form.
  • vilazodone docusate the relationship was used that 1.846 mg of vilazodone docusate are equivalent to 0.92 mg of vilazodone (same concentration as the reference medicine).
  • the tablets were obtained by the direct compression process, with good processability characteristics.
  • the tablets presented physical characteristics of hardness, friability and disintegration suitable for a pharmaceutical form.
  • the IFA (27.690g), a lactose fraction (30g) and microcrystalline cellulose (30g) were homogenized manually with rotational movements for 5 - 15 minutes (mixture 1).
  • colloidal silicon dioxide (1.05g) and the remainder of lactose (30g) were added to mixture 1, being homogenized for another 5-15 minutes (mixture 2).
  • colloidal magnesium stearate 1.5g was added to mixture 2 and homogenized for another 3 - 5 minutes (final mixture).
  • the final mixture was added to the feeder of the compression simulator previously assembled with an EU-B circular die and a 6 mm biconcave circular punch without crease.
  • the tablets were obtained with a Default Cycle - 1 compression cycle, machine speed of 25% and compression forces of 4KN to 12KN.
  • the resulting ejection forces during the process were ⁇ 100N, indicating good processability of the bulk with low adhesion to the tooling.
  • Disintegration was carried out in water at a temperature of 37 °C ⁇ 1 °C and the results showed disintegration times of less than 5 minutes for all tablets evaluated, regardless of hardness.
  • the friability test which makes it possible to determine the resistance of the tablets to abrasion, was carried out with 20 tablets in a friability meter adjusted to operate at a speed of 25 rotations per minute for 4 minutes. The difference between the initial and final weight of the tablets was less than 0.5%, indicating low friability, in accordance with Brazilian pharmacopoeia guidelines.
  • composition and process described in the embodiment exclude the presence of coating agent(s) in the tablets, which can be an optional additive process after the compression step.
  • the coating as long as it does not alter the characteristics of the immediate release pharmaceutical form, can be used to mask flavor, facilitate swallowing, improve aesthetic characteristics, for better identification of the brand, among others.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un sel de docusate de vilazodone, son procédé d'obtention, une composition pharmaceutique comprenant ce sel de docusate de vilazodone, ainsi que son utilisation.
PCT/BR2022/050092 2022-03-16 2022-03-16 Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation WO2023173182A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/BR2022/050092 WO2023173182A1 (fr) 2022-03-16 2022-03-16 Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/BR2022/050092 WO2023173182A1 (fr) 2022-03-16 2022-03-16 Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation

Publications (1)

Publication Number Publication Date
WO2023173182A1 true WO2023173182A1 (fr) 2023-09-21

Family

ID=88021862

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/BR2022/050092 WO2023173182A1 (fr) 2022-03-16 2022-03-16 Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation

Country Status (1)

Country Link
WO (1) WO2023173182A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014028473A1 (fr) * 2012-08-13 2014-02-20 Assia Chemical Industries Ltd. Nouveaux sels de vilazodone et leurs formes à l'état solide
WO2014049609A2 (fr) * 2012-09-26 2014-04-03 Cadila Healthcare Limited Nouveaux sels de vilazodone
WO2014049612A2 (fr) * 2012-09-27 2014-04-03 Msn Laboratories Limited Procédés et polymorphes de 5-[4-[4-(5-cyano-1h-indol-3-yl) butyl]-1-pipérazinyl]-2-benzofuran carboxamide et ses sels

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014028473A1 (fr) * 2012-08-13 2014-02-20 Assia Chemical Industries Ltd. Nouveaux sels de vilazodone et leurs formes à l'état solide
WO2014049609A2 (fr) * 2012-09-26 2014-04-03 Cadila Healthcare Limited Nouveaux sels de vilazodone
WO2014049612A2 (fr) * 2012-09-27 2014-04-03 Msn Laboratories Limited Procédés et polymorphes de 5-[4-[4-(5-cyano-1h-indol-3-yl) butyl]-1-pipérazinyl]-2-benzofuran carboxamide et ses sels

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PEDRO SÓNIA N., R. FREIRE CARMEN S., SILVESTRE ARMANDO J. D., FREIRE MARA G.: "The Role of Ionic Liquids in the Pharmaceutical Field: An Overview of Relevant Applications", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 21, pages 8298, XP093092548, DOI: 10.3390/ijms21218298 *
SUTAR YOGESH, FULTON SOPHIE R., PAUL SAGARKUMAR, ALTAMIRANO SOPHIE, MHATRE SUSMIT, SAEED HIWA, PATEL PRATIKKUMAR, MALLICK SUDIPTA,: "Docusate-Based Ionic Liquids of Anthelmintic Benzimidazoles Show Improved Pharmaceutical Processability, Lipid Solubility, and in Vitro Activity against Cryptococcus neoformans", ACS INFECTIOUS DISEASES, AMERICAN CHEMICAL SOCIETY, US, vol. 7, no. 9, 10 September 2021 (2021-09-10), US , pages 2637 - 2649, XP093092547, ISSN: 2373-8227, DOI: 10.1021/acsinfecdis.1c00063 *

Similar Documents

Publication Publication Date Title
US9562024B2 (en) Vortioxetine salt and crystal thereof, their preparation method, pharmaceutical compositions and usage
JP5702494B2 (ja) ピタバスタチンカルシウムの新規な結晶質形態
EP2909191B1 (fr) Système cristallin multicomposant comprenant du nilotinib et des formateurs de co-cristal sélectionnés
JP6211072B2 (ja) ダサチニブと、選択された共結晶形成剤とを含んでなる多成分結晶
ES2562843T3 (es) Forma IV de clorhidrato de ivabradina
BR112015006075B1 (pt) Composto cristalino, composição farmacêutica, uso do composto cristalino, hidrato cristalino do bromidrato de vortioxetina, método para a preparação do hidrato cristalino de bromidrato de vortioxetina, método para a preparação do composto cristalino e uso do hidrato cristalino de bromidrato de vortioxetina
US20100010098A1 (en) Polymorphs of rasagiline hydrochloride
DK3294719T3 (en) VORTIOXETIN-pyroglutamate
JP2016525528A (ja) 非晶質形態のダサチニブの塩
WO2015054804A1 (fr) Forme solide d'enzalutamide, procédé de préparation et utilisation associée
AU2014286308B2 (en) 1-[2-(2,4-dimethylphenylsulfanyl) phenyl]piperazine acetate in crystalline form
WO2023173182A1 (fr) Sel de docusate de vilazodone, procédé d'obtention, composition pharmaceutique et utilisation
JP7212958B2 (ja) バルベナジントシル酸塩の結晶形及びその製造方法並びに用途
JP2023025193A (ja) キナゾリン誘導体を含有する固形製剤
CN105367551A (zh) 达比加群酯乙醇酸盐及其制备方法和应用
RU2600929C2 (ru) Полиморфы дейтерированной омега-дифенилмочевины или ее солей
JP2020059724A (ja) アルツハイマー病の処置用のｎ−［２−（６−フルオロ−１ｈ−インドール−３−イル）エチル］−３−（２，２，３，３−テトラフルオロプロポキシ）ベンジルアミン塩酸塩の新規な多形形態
US9981912B2 (en) Cocrystal of lorcaserin, preparation methods, pharmaceutical compositions and uses thereof
WO2015096119A1 (fr) Sels de lorcasérine et leurs cristaux, leurs procédés de préparation et utilisations
KR20200139127A (ko) 설파살라진 염 조성물 및 이의 사용 방법
CN110582279A (zh) 2-(6-甲基-吡啶-2-基)-3-基-[6-酰胺基-喹啉-4-基]-5,6-二氢-4H-吡咯并[1,2-b]吡唑的共晶，其制备方法和药物组合物
EP3184516A1 (fr) Complexe d'inclusion crystallin de mirabegron avec beta-cyclodextrine
Vyas et al. Enhancement of Physicochemical and Pharmacokinetic Characteristics of Ranolazine drug substance using Cocrystalization Technique
EP4251162A1 (fr) Procédé de fabrication amélioré pour les formulations comprenant une forme h de solvate de butanol de hbr de vortioxétine
CN105348260A (zh) 达比加群酯氢溴酸盐及其制备方法和应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22931266

Country of ref document: EP

Kind code of ref document: A1