WO2015019256A1 - Composition pharmaceutique de vilazodone et procédés de préparation de celle-ci - Google Patents

Composition pharmaceutique de vilazodone et procédés de préparation de celle-ci Download PDF

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Publication number
WO2015019256A1
WO2015019256A1 PCT/IB2014/063595 IB2014063595W WO2015019256A1 WO 2015019256 A1 WO2015019256 A1 WO 2015019256A1 IB 2014063595 W IB2014063595 W IB 2014063595W WO 2015019256 A1 WO2015019256 A1 WO 2015019256A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
vilazodone
composition according
μιη
tablets
Prior art date
Application number
PCT/IB2014/063595
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English (en)
Inventor
Surajit Das
Abhishek Srivastava
Mukesh Kumar Garg
Ajay Kumar Singla
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2015019256A1 publication Critical patent/WO2015019256A1/fr

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Classifications

    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to pharmaceutical compositions comprising vilazodone and one or more non-ionic surfactants. It also relates to processes for the preparation of said pharmaceutical compositions and methods of treating and/or preventing central nervous system disorders by administering said pharmaceutical compositions.
  • Vilazodone hydrochloride disclosed in U.S. Patent No. 5,532,241, is chemically designated as 2-benzofurancarboxamide, 5-[4-[4-(5-cyano-lH-indol-3-yl)butyl]-l- piperazinyl]-, hydrochloride (1 : 1).
  • Vilazodone hydrochloride is a selective serotonin reuptake inhibitor and a 5HTIA receptor partial agonist. It is indicated for the treatment of major depressive disorder.
  • U.S. Patent No. 7,834,020 discloses fifteen crystalline modifications of vilazodone hydrochloride designated as Form I through Form XV. It also discloses conventional forms of administration such as tablets and capsules.
  • PCT Publication No. WO 2012/131706 discloses the amorphous form of vilazodone hydrochloride.
  • PCT Publication No. WO 2013/078361 discloses several other polymorphic forms of vilazodone hydrochloride.
  • the present invention relates to pharmaceutical compositions of vilazodone which are bioequivalent to commercially available Viibryd ® tablets.
  • the present invention includes pharmaceutical compositions of vilazodone and one or more non-ionic surfactants. It further includes pharmaceutical compositions of vilazodone and one or more non-ionic surfactants encapsulated within an inert carrier.
  • the present invention includes processes for the preparation of said pharmaceutical compositions. It further includes a method of treating and/or preventing central nervous system disorders by administering said pharmaceutical compositions.
  • the desired dissolution profile is a prerequisite for the development of a regulatory compliant drug product.
  • a surfactant for enhancing the dissolution of the drugs in compositions is known, the choice of a particular surfactant is critical.
  • the scientists of the present invention have found that the use of a particular non-ionic surfactant in vilazodone compositions enhances the rate and extent of dissolution and provides the desired dissolution profile. Further, it has been found that the non-ionic surfactant encapsulated within an inert carrier provides a free-flowing powder which can be easily formulated into the pharmaceutical compositions. Also, because particle size plays a key role in the solubility and dissolution profile of a drug, the present invention uses micronized vilazodone particles to achieve the desired release profile.
  • a first aspect of the present invention provides a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants.
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the non-ionic surfactant is encapsulated within an inert carrier.
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the vilazodone particles have a D50 range of about 0.1 ⁇ to about 20 ⁇ .
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the vilazodone particles have a D 90 range of about 0.5 ⁇ to about 40 ⁇ .
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the vilazodone particles have D10 range of about 0.05 ⁇ to about 10 ⁇ .
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein more than 40% w/w of vilazodone dissolves within 30 minutes in 0.1N HC1, in a USP type II apparatus.
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the pharmaceutical composition is a stable composition.
  • a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the composition is bioequivalent to Viibryd ® tablets when bioavailability studies are conducted in humans.
  • a second aspect of the present invention provides a process for the preparation of a pharmaceutical composition of vilazodone, wherein the process comprises the steps of:
  • step (b) directly compressing the blend of step (a) to form tablets
  • a third aspect of the present invention provides a process for the preparation of a pharmaceutical composition of vilazodone, wherein the process comprises the steps of:
  • step (b) granulating the blend of step (a);
  • step (c) blending the granules of step (b) with one or more pharmaceutically
  • step (d) compressing the blend of step (c) to form tablets
  • a fourth aspect of the present invention provides a method of treating and/or preventing a central nervous system disorder by administering a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants.
  • a method of treating and/or preventing a central nervous system disorder by administering a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the central nervous system disorder is selected from major depressive disorder, anxiety disorders, bipolar disorders, mania, dementia, eating disorders, sleeping disorders, psychiatric disorders, cerebral infarct, tension, and any combination thereof.
  • a method of treating and/or preventing central nervous system disorder by administering a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the central nervous system disorder is major depressive disorder.
  • a method of treating and/or preventing central nervous system disorders by administering a pharmaceutical composition comprising vilazodone and one or more non-ionic surfactants, wherein the method comprises co-administration of additional drugs acting on the central nervous system.
  • vilazodone refers to 2-benzofurancarboxamide, 5-[4- [4-(5- cyano-lH-indol-3-yl)butyl]-l-piperazinyl] . It further includes salts, polymorphs, hydrates, solvates, prodrugs, chelates, and complexes thereof.
  • the preferred salt of vilazodone is vilazodone hydrochloride.
  • the pharmaceutical compositions of the present invention comprise vilazodone in an amount of from about 1% w/w to about 30% w/w, preferably from about 5% w/w to about 20% w/w of the total composition.
  • Vilazodone hydrochloride may be used in the pharmaceutical composition in strengths of 10 mg, 20 mg, and 40 mg of vilazodone.
  • the vilazodone hydrochloride used in the pharmaceutical composition may encompass any known polymorphs at the time of the invention. It may also encompass the amorphous form of vilazodone hydrochloride.
  • the pharmaceutical composition of the present invention comprises vilazodone hydrochloride Form IV.
  • D50 refers to a particle diameter at which 50% of the particles have diameters which are greater or smaller than the given value.
  • the present invention includes vilazodone particles having a D 50 range of about 0.1 ⁇ to about 20 ⁇ , in particular from about 1 ⁇ to about 10 ⁇ .
  • D 90 refers to a particle diameter at which 90% of the particles have diameters which are smaller than the given value.
  • the present invention includes vilazodone particles having a D 90 range of about 0.5 ⁇ to about 40 ⁇ , in particular, about 5 ⁇ to about 20 ⁇ .
  • Dio refers to a particle diameter at which 10% of the particles have diameters which are smaller than the given value.
  • the present invention includes vilazodone particles having a Di 0 range of about 0.05 ⁇ to about 10 ⁇ , in particular from about 0.1 ⁇ to about 5 ⁇ .
  • Di 0 , D 50 and D 90 values given above refer to a discrete number, e.g., 1 ⁇ . Therefore, by providing a range for Di 0 it should be understood that the Di 0 particle diameter is a discrete value within that range.
  • the size reduction or micronization of vilazodone may be carried out by using any of the conventional mills such as air jet mills, ball mills, colloid mills, grinding mills, roller mills, or impact mills.
  • the particle size is reduced by a ball mill.
  • the particle size may be determined by any known technique such as a sieve analyzer, electrical conductance instruments such as a coulter counter, and laser diffraction particle size analyzer such as a Malvern ® instrument.
  • the particle size is determined by a Malvern ® instrument.
  • stable refers to chemical as well as physical stability. Chemical stability means maintaining the original formulation specifications, and physical stability means that there is no change in the polymorphic form determined by X-ray powder diffraction after exposure to a relative humidity of 75% at 40°C or relative humidity of 60% at 25°C, for a period of at least about three months to the extent necessary for sale and use of the composition.
  • unmicronized and micronized vilazodone hydrochloride particles show polymorphic stability, as there is no conversion of polymorphic forms during micronization.
  • non-ionic surfactant refers to a water-soluble surfactant which is liquid or semi-solid at 25°C Suitable non-ionic surfactants are selected from the group consisting of polyoxyethyl-sorbitan-fatty acid esters such as polysorbates; ethers of sugars such as ethers of lactose, sucrose, xylose, mannitol, or xylitol; ethoxylated fatty alcohols; fatty acids and their salts; ethoxylated fatty acids; polyglyceryl esters;
  • copolymers of propylene oxide and of ethylene oxide phospholipids or lecithins; amino acid fatty chain acrylates; triglycerides of plant or synthetic origin and their ethoxylated derivatives such as polyoxyl 35 castor oil and polyoxyl 40 hydrogenated castor oil;
  • acetylated monoglycerides sodium lauryl sulphate and its derivatives; taurocholic acid; or mixtures thereof.
  • the preferred non-ionic surfactant is a polysorbate.
  • carrier refers to the particulate or porous material having an appropriate surface area on which the drug may be encapsulated
  • Suitable carriers are selected form the group consisting of magnesium aluminum silicate, aluminum silicate, calcium silicate, magnesium silicate, magnesium trisilicate, sodium magnesium silicate, lithium magnesium silicate, zirconium silicate, attapulgite, bentonite, fuller's earth, hectorite, kaolin, montmorillonite, pyrophyllite, zeolite, calcium carbonate, calcium phosphate, calcium gluconate, magnesium gluconate, manganese gluconate, calcium diphosphate, silicon dioxide, microcrystalline celluloses, sugars such as lactose, sorbitol, mannitol, xylitol, or maltitol, or mixtures thereof.
  • encapsulated refers to a non-ionic surfactant homogeneously distributed within the inert earner particles.
  • microencapsulated refers to very tiny droplets of liquid or semi-solid particles of a non-ionic surfactant surrounded or coated with inert carrier particles.
  • adhered refers to adherence of a non-ionic surfactant onto the surface of the inert carrier particles without penetrating inside the inert carrier particles.
  • Bioequivalence is established by comparing pharmacokinetic parameters, for example AUC and C max , of the present invention with Viibryd ® tablets in healthy human subjects.
  • AUC refers to the area under the time/plasma concentration curve after the administration of the vilazodone dosage form to healthy human subjects.
  • C m ax refers to the maximum concentration of vilazodone in the blood following the administration of the vilazodone dosage form to healthy human subjects.
  • Bioequivalence is defined to mean the term used by the drug approval agencies, such as the US Food and Drug Administration: "the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.” This is typically understood to mean that the test drug product is within +25% and -20% of the reference drug product for AUC and Cma X , for example as explained in the US FDA's various bioequi valence guidance documents for oral tablets and capsules, which are incorporated herein by reference.
  • the non-ionic surfactant is encapsulated within an inert carrier using any suitable conventional processes such as dissolving the non-ionic surfactant in a suitable solvent, combining the inert carrier, and removing the solvent by filtration and/or evaporation.
  • any suitable conventional processes such as dissolving the non-ionic surfactant in a suitable solvent, combining the inert carrier, and removing the solvent by filtration and/or evaporation.
  • mechanical homogenization or spray drying processes can also be used for preparing the encapsulated non-ionic surfactant.
  • SEPITRAP ® 80 comprises from about 35% w/w to about 55% w/w of polysorbate 80 and from about 45% w/w to about 65% w/w of magnesium aluminum silicate.
  • the pharmaceutical composition of the present invention comprises SEPITRAP ® 80 in an amount of from about 0.1% w/w to about 10% w/w of the total composition.
  • composition means a composition which is selected from the group consisting of tablets, capsules, pellets, pills, caplets, and granules, in particular tablets.
  • pharmaceutically acceptable excipient includes excipients that may be added intragranularly and/or extragranularly in the pharmaceutical compositions.
  • the pharmaceutically acceptable excipients include fillers, binders, lubricants, disintegrants, coloring agents, plasticizers, and opacifiers.
  • Suitable fillers are selected from the group consisting of lactose monohydrate, lactose anhydrous, pregelatinized starch, calcium carbonate, calcium phosphate dibasic, calcium phosphate tribasic, calcium sulphate, kaolin, starch, or mixtures thereof.
  • Suitable binders are selected from the group consisting of methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, or mixtures thereof.
  • Suitable lubricants are selected from the group consisting of colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, talc, hydrogenated castor oil, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax, or mixtures thereof.
  • Suitable disintegrants are selected from the group consisting of sodium starch glycolate, croscarmellose, pregelatinized starch, microcrystalline cellulose, calcium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, magnesium silicate, aluminum silicate, or mixtures thereof.
  • Coloring agents include any FDA approved color for oral use.
  • Suitable plasticizers are selected from the group consisting of triethyl citrate, dibutyl sebacate, acetylated triacetin, tributyl citrate, glycerol tributyrate, monoglyceride, rapeseed oil, olive oil, sesame oil, acetyl tributyl citrate, acetyl triethyl citrate, glycerin sorbitol, diethyl oxalate, diethyl phthalate, diethyl malate, diethyl fumarate, dibutyl succinate, diethylmalonate, dioctyl phthalate, or mixtures thereof.
  • Suitable opacifiers are selected from the group consisting of titanium dioxide, manganese dioxide, iron oxide, silicon dioxide, or mixtures thereof.
  • the present invention provides a process for the preparation of a pharmaceutical composition, wherein the process comprises the steps of:
  • step (b) directly compressing the blend of step (a) to form tablets
  • the present invention also provides a process for the preparation of a
  • composition wherein the process comprises the steps of:
  • step (b) granulating the blend of step (a);
  • step (c) blending the granules of step (b) with one or more pharmaceutically
  • step (d) compressing the blend of step (c) to form tablets
  • the non-ionic surfactant may be encapsulated within an inert carrier and then the encapsulated surfactant may be used in the process for the preparation of a pharmaceutical composition.
  • the vilazodone used in the process for the preparation of the pharmaceutical composition may comprise micronized vilazodone hydrochloride particles.
  • the granulation may be carried out by using either a wet granulation or dry granulation process.
  • Wet granulation may include rapid mixer granulation or fluid bed granulation.
  • Dry granulation may involve the formation of slugs or the use of a chilsonator.
  • Suitable solvents used for wet granulation include water, ethanol, methanol, isopropyl alcohol, dichloromethane, acetone, or mixtures thereof.
  • the pharmaceutical composition of the present invention is further coated with one or more functional or non-functional coatings.
  • the pharmaceutical composition is coated with one or more non-functional coatings.
  • the coating layers may comprise one or more film-forming polymers and coating additives.
  • film-forming polymers examples include ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, waxes, and methacrylic acid polymers such as Eudragit ® and the like.
  • ethylcellulose hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, waxes, and methacrylic acid polymers such as Eudragit ® and the like.
  • methacrylic acid polymers such as Eudragit ® and the like.
  • Coating additives may be selected from the group consisting of binders, plasticizers, coloring agents, and lubricants.
  • granulating fluid/solvents for coating include acetone, ethanol, isopropyl alcohol, methylene chloride, or combinations thereof.
  • Coating may be performed by applying the coating composition as a
  • Microcrystalline cellulose and colloidal silicon dioxide were sifted and mixed
  • Micronized vilazodone hydrochloride was sifted and mixed with a portion of lactose monohydrate.
  • step 1 The mixtures from step 1, step 2, and step 3 were mixed together.
  • step 4 The mixture of step 4 was lubricated with sifted magnesium stearate.
  • step 5 The final blend of step 5 was compressed.
  • step 6 The core tablets of step 6 were coated with the coating dispersion of step 7.
  • the pharmaceutical composition prepared according to the above example provides an in-vitro drug-release comparable to the innovator Viibryd ® tablet.

Abstract

La présente invention concerne des compositions pharmaceutiques contenant de la vilazodone et un ou plusieurs tensioactifs non ioniques. L'invention concerne également des procédés de préparation desdites compositions pharmaceutiques, ainsi qu'une méthode de traitement et/ou de prévention d'un trouble du système nerveux central par l'administration desdites compositions pharmaceutiques.
PCT/IB2014/063595 2013-08-06 2014-07-31 Composition pharmaceutique de vilazodone et procédés de préparation de celle-ci WO2015019256A1 (fr)

Applications Claiming Priority (2)

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IN2348DE2013 2013-08-06
IN2348/DEL/2013 2013-08-06

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WO2015019256A1 true WO2015019256A1 (fr) 2015-02-12

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106580914A (zh) * 2017-02-27 2017-04-26 佛山市弘泰药物研发有限公司 一种盐酸维拉佐酮软胶囊及其制备方法
CN110604723A (zh) * 2018-06-14 2019-12-24 北京万全德众医药生物技术有限公司 盐酸维拉佐酮口崩片及其制备方法
US10688090B2 (en) 2016-11-02 2020-06-23 Sunshine Lake Pharma Co., Ltd. Vilazodone inclusion complexes, compositions and preparation thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5532241A (en) 1993-09-30 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Piperidines and piperazines
US7834020B2 (en) 2001-06-19 2010-11-16 Merck Patent Gesellschaft Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride
WO2012131706A1 (fr) 2011-03-20 2012-10-04 Cadila Healthcare Limited Forme amorphe du chlorhydrate de vilazodone et son procédé de préparation
WO2013078361A1 (fr) 2011-11-23 2013-05-30 Assia Chemical Industries Ltd. Formes à l'état solide de vilazodone et de chlorhydrate de vilazodone

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5532241A (en) 1993-09-30 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Piperidines and piperazines
US7834020B2 (en) 2001-06-19 2010-11-16 Merck Patent Gesellschaft Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride
WO2012131706A1 (fr) 2011-03-20 2012-10-04 Cadila Healthcare Limited Forme amorphe du chlorhydrate de vilazodone et son procédé de préparation
WO2013078361A1 (fr) 2011-11-23 2013-05-30 Assia Chemical Industries Ltd. Formes à l'état solide de vilazodone et de chlorhydrate de vilazodone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "VIIBRYD(TM) (vilazodone hydrochloride) Tablets", 2011, pages 1 - 13, XP055144766, Retrieved from the Internet <URL:http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022567s000lbl.pdf> [retrieved on 20141007] *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10688090B2 (en) 2016-11-02 2020-06-23 Sunshine Lake Pharma Co., Ltd. Vilazodone inclusion complexes, compositions and preparation thereof
US11517569B2 (en) 2016-11-02 2022-12-06 Sunshine Lake Pharma Co., Ltd. Vilazodone inclusion complexes, compositions and preparation thereof
CN106580914A (zh) * 2017-02-27 2017-04-26 佛山市弘泰药物研发有限公司 一种盐酸维拉佐酮软胶囊及其制备方法
CN110604723A (zh) * 2018-06-14 2019-12-24 北京万全德众医药生物技术有限公司 盐酸维拉佐酮口崩片及其制备方法

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