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WO2009150665A1 - Compositions pharmaceutiques à désintégration orale d’escitalopram et de sels de celui-ci - Google Patents

Compositions pharmaceutiques à désintégration orale d’escitalopram et de sels de celui-ci Download PDF

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Publication number
WO2009150665A1
WO2009150665A1 PCT/IN2009/000291 IN2009000291W WO2009150665A1 WO 2009150665 A1 WO2009150665 A1 WO 2009150665A1 IN 2009000291 W IN2009000291 W IN 2009000291W WO 2009150665 A1 WO2009150665 A1 WO 2009150665A1
Authority
WO
WIPO (PCT)
Prior art keywords
orally disintegrating
escitalopram
pharmaceutical composition
salts
composition according
Prior art date
Application number
PCT/IN2009/000291
Other languages
English (en)
Inventor
Avinash Krishnaji Velhal
Sunil Anantrao Mirajkar
Virendra Ramkrupal Kuril
Ninad Deshpanday
Original Assignee
Lupin 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 Lupin Limited filed Critical Lupin Limited
Publication of WO2009150665A1 publication Critical patent/WO2009150665A1/fr

Links

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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone

Definitions

  • the present invention relates to orally disintegrating pharmaceutical compositions of Escitalopram and salts thereof and methods for the manufacture of such orally disintegrating pharmaceutical compositions.
  • Escitalopram is a selective, centrally acting serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor. It is marketed as Lexapro® tablets in the United States for the treatment of Major depressive disorder and Generalized anxiety disorder.
  • Escitalopram was first disclosed in U.S. Pat. No. 4,943,590.
  • Orally disintegrating pharmaceutical compositions including granules, tablets are convenient oral delivery systems designed to disintegrate rapidly upon contact with aqueous fluids, e.g. water or saliva, to form a dispersion, which can be swallowed easily.
  • Orally disintegrating pharmaceutical compositions are particularly advantageous for patients e.g. pediatric or geriatric patients, having difficulty in swallowing conventional tablets or capsules, or for individuals who may not have difficulty in swallowing but may have an aversion to swallowing conventional tablets or capsules.
  • Orally disintegrating pharmaceutical compositions are also convenient under circumstances in which taking an oral dosage form with water may be inconvenient (e.g. while working or traveling).
  • Conventional orally disintegrating tablets are typically formed by compression (e.g., in a tablet press). It is desirable for such tablets to have sufficiently high hardness and sufficiently low friability to provide structural stability for transportation and storage. Low friability (which is measured based on the percent tablet weight loss after a certain number of revolutions in a friabilator) is desirable in that it is generally indicative of high tablet strength. High porosity of the tablet structure also is desirable in that it allows fluids (e.g., aqueous or bodily fluids, e.g.; water or saliva) to be drawn or "wicked" from the external environment and into the interstices of the tablet structure, thereby promoting rapid and effective disintegration.
  • fluids e.g., aqueous or bodily fluids, e.g.; water or saliva
  • US 2007/0021499 Al discloses orodispersible tablets prepared by mixing water soluble filler and active pharmaceutical ingredient at a temperature above, around or slightly below the melting point of the active pharmaceutical ingredient followed by cooling to a temperature below 40° C and mixing cooled mass with other excipients and compressing it into tablets with a hardness of at least 22 N.
  • US 2007/0092564 Al discloses orally disintegrating tablets prepared with pullalan as binder and glycine as disintegrant comprising quickly freeze-drying soluble composition, useful for providing oral-drug delivery of various drugs in disease treatment.
  • US 2002/0142034 Al discloses an orally disintegrable tablet comprising (i) fine granules composition coated by an enteric coating layer and (ii) an additive, having a superior disintegrability or dissolution in the oral cavity.
  • the present invention provides orally disintegrating pharmaceutical compositions of a)
  • Escitalopram or salts thereof as an active ingredient b) diluent(s) selected from the group consisting of cellulose derivatives such as macrocrystalline cellulose and the like, mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose, dicalcium phosphate and their derivatives thereof; c) disintegrating agent(s) and d) optionally one or more suitable pharmaceutically acceptable excipient(s).
  • cellulose derivatives such as macrocrystalline cellulose and the like, mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose, dicalcium phosphate and their derivatives thereof
  • disintegrating agent(s) and d) optionally one or more suitable pharmaceutically acceptable excipient(s) optionally one or more suitable pharmaceutically acceptable excipient(s).
  • Yet another object of the present invention provides orally disintegrating pharmaceutical compositions comprising Escitalopram and salts thereof, as an active ingredient in an amount from about 1% to about 25% by total weight of the composition.
  • Yet another object of the present invention provides orally disintegrating pharmaceutical compositions comprising Escitalopram and/or salts thereof, wherein orally disintegrating pharmaceutical composition is a tablet.
  • Yet another object of the present invention provides orally disintegrating tablet comprising Escitalopram and/or salts thereof having low friability not more than 0.5%.
  • Yet another object of the present invention provides orally disintegrating tablet comprising Escitalopram and/or salts thereof having hardness not less than IO N.
  • Yet another object of the present invention provides a method of producing orally disintegrating pharmaceutical compositions by conventional methods known in the art.
  • the method of producing orally disintegrating pharmaceutical compositions comprises direct compression, dry granulation or wet granulation.
  • Dry granulation method comprises mixing of Escitalopram and/or salts with diluent(s) and optionally with other suitable pharmaceutically acceptable excipients, passing this blend through roll compaction, milling this compacted mass through suitable sieves, adding disintegrant(s) and other suitable pharmaceutically acceptable excipients and finally thus obtained granules can be filled into a suitable container or can be compressed into an orally disintegrating tablet.
  • the method of producing orally disintegrating pharmaceutical compositions preferably comprises Escitalopram and/or salts thereof, diluents, disintegrating agents; optionally other suitable pharmaceutically acceptable excipients, and solvent(s), to form a wet granulate.
  • the wet granulate is dried, to produce a dry granulate comprising the Escitalopram and/or salts thereof.
  • the wet granulate and/or dry granulate can be blended with other suitable pharmaceutically acceptable excipients. These granules can be filled into a suitable container or can be compressed into an orally disintegrating tablet.
  • the most preferred method of manufacturing of an orally disintegrating pharmaceutical compositions comprising wet granulation of Escitalopram and/or salts thereof, diluents, disintegrating agents, binders, by fluidized bed processor.
  • the orally disintegrating pharmaceutical compositions of the invention typically contain 1% to 25% w/w Escitalopram as base.
  • the orally disintegrating pharmaceutical compositions of the invention optionally may comprise pharmaceutically acceptable complexes, salts, polymorphs, hydrates, and solvates, of Escitalopram, preferably Escitalopram oxalate.
  • the present invention provides orally disintegrating pharmaceutical compositions comprising Escitalopram and salts thereof, as an active ingredient, diluent(s), a disintegrating agent(s) and optionally other suitable pharmaceutically acceptable excipient(s)
  • orally disintegrating pharmaceutical compositions refers to the ability of a pharmaceutical composition (e.g., granules, a tablet for oral administration) to disintegrate rapidly when contacted with a fluid, particularly an aqueous fluid (e.g., water, bodily fluids (e.g., saliva), and the like), to form a suspension, slurry or dispersion, which facilitates administration of the contents of the composition (e.g., by forming a suspension, slurry or dispersion, which is easily swallowed).
  • a pharmaceutical composition e.g., granules, a tablet for oral administration
  • a fluid particularly an aqueous fluid (e.g., water, bodily fluids (e.g., saliva), and the like)
  • a suspension, slurry or dispersion e.g., water, bodily fluids (e.g., saliva), and the like
  • the orally disintegrating pharmaceutical compositions of the present invention can either be granules alone that can be filled into a suitable container preferably a sachet or granules can further be compressed into a tablet.
  • oral granular formulations such as granules, powders and fine granules can also be prepared.
  • orally includes the region within the interior of the mouth, including, but not limited to, the buccal cavity (e.g., anterior to the teeth and gums) as well as the sublingual and supralingual spaces, and the like. .
  • compositions of the present invention preferably disintegrates within about 120 seconds or less, when contacted with an aqueous fluid (e.g., water, saliva, or a buffered solution), to form a slurry, a dispersion or a suspension, which can be administered
  • an aqueous fluid e.g., water, saliva, or a buffered solution
  • the disintegration time of the pharmaceutical compositions of the present invention can range from within about 2 seconds to within about 120 seconds, e.g., from within about 2 seconds to within about 60 seconds, or from within about 2 seconds to within about 30 seconds, as measured in by the Standard USP Disintegration Test Apparatus.
  • compositions of the present invention more preferably disintegrates from within about 2 seconds to within about 30 seconds, and still more preferably from within about 2 seconds to within about 20 seconds, and most preferably from within about 2 seconds to within about 10 seconds, as measured in by the Standard USP Disintegration Test Apparatus.
  • the friability of the orally disintegrating tablet of the present invention preferably is not more than about 1 %, more preferably about 0.8 %, and most preferably about 0.5 %.
  • Hardness refers to the diametral breaking strength as measured by conventional pharmaceutical tablet hardness determination methods, which are well known in the art. A higher hardness value, sometimes measured in Newtons (N), generally is indicative of higher diametric strength.
  • the hardness of the tablet of the present invention preferably ranges from about 35 N to about 30 N, and more preferably from about 25 N to about 20 N, and most preferably from about 15 N to about IO N.
  • Diluents may be for example various cellulose derivatives such as microcrystalline cellulose and the like, mannitol, lactose, dextrose, sorbitol, starch, xylitol, maltose, dicalcium phosphate and their derivatives thereof.
  • Disintegrants may be for example starch or its derivative like pregelatinised starch, sodium carboxymethyl starch, sodium starch glycolate and the like, various cellulose derivatives crosslinked sodium carboxy methyl cellulose, low substitute hydroxypropyl cellulose, cross carmellose calcium and the like, crosspovidone and the like, alginic acid and various ion exchange resins.
  • the other suitable pharmaceutically acceptable excipients of the compositions of the present invention can also include other materials such as binding agents, taste masking agents, anti- adherents, lubricants, sweeteners, flavors and co-processed excipients.
  • Binding agents may be, for example, various cellulose derivatives such as low molecular weight hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and the like, methacrylate copolymers, amino alkyl methacrylate copolymers and the like, povidone and the like, sodium alginate and the like.
  • Taste masking agent may be, for example, various cellulose derivatives such as low molecular weight hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and the like, methacrylate copolymers, amino alkyl methacrylate copolymers and the like, povidone and the like.
  • Antiadherents may be, for example, colloidal silicon dioxide, talc and the like.
  • Lubricants may be, for example, talc, magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate and the like.
  • Sweeteners may be for example aspartame, acesulfam potassium, sucralose, xylitol, saccharine, saccharine potassium, sugars and the like.
  • Flavors may be for example mint flavors, orange flavor, lemon flavor, banana flavor, strawberry flavor, magnasweet, grape flavor and the like.
  • Solvents may be for example aqueous or non-aqueous or their mixtures thereof.
  • Nonaqueous solvents for example may be isopropyl alcohol, acetone and the like.
  • Co-processed excipients may be for example CELLACTOSE ® 80 (75% lactose monohydrate & 25% cellulose powder), StarLac (85% Lactose monohydrate & 15% Maize Starch), FormaxTM (Calcium carbonate / Sorbitol (70:30), Ludiflash ® (Mannitol, crospovidone, polyvinyl acetate and povidone).
  • step 1 blend and mill it through 30 # sieve.
  • step 3 Add microcrystalline cellulose, Croscarmellose sodium, Banana Flavor and Aspartame to blend of step 3.
  • step 1 Add microcrystalline cellulose, Mint Flavor and Aspartame to blend of step 1.
  • step 3 Mix and finally lubricate blend of step 2 with talc and magnesium stearate and compress the resultant blend.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pharmaceutique à désintégration orale comprenant de l’escitalopram ou des sels de celui-ci en tant que principe actif ; un/des diluant(s) choisi(s) dans le groupe constitué de dérivés de cellulose tels que la cellulose microcristalline et similaire, le mannitol, le lactose, le dextrose, le sorbitol, l’amidon, le xylitol, le maltose, le phosphate dicalcique et leurs dérivés ; un/des agent(s) délitant(s) et éventuellement un ou plusieurs excipient(s) pharmaceutiquement acceptable(s) adapté(s).
PCT/IN2009/000291 2008-06-09 2009-05-18 Compositions pharmaceutiques à désintégration orale d’escitalopram et de sels de celui-ci WO2009150665A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1003/KOL/2008 2008-06-09
IN1003KO2008 2008-06-09

Publications (1)

Publication Number Publication Date
WO2009150665A1 true WO2009150665A1 (fr) 2009-12-17

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20120106A1 (it) * 2012-01-30 2013-07-31 Carthesia S A S Pastiglie liofilizzate di escitalopram ossalato per somministrazione sublinguale
WO2013114416A1 (fr) 2012-01-30 2013-08-08 Carthesia S.A.S. Comprimés lyophilisés d'oxalate d'escitalopram destinés à être administrés par voie sublinguale
WO2014184663A3 (fr) * 2013-05-15 2015-01-22 Apr Applied Pharma Research Sa Formulations de médicaments dispersables par voie orale
CN104523638A (zh) * 2014-11-28 2015-04-22 浙江华海药业股份有限公司 含有草酸艾司西酞普兰的片剂及其制备方法
CN106038501A (zh) * 2016-06-30 2016-10-26 北京万全德众医药生物技术有限公司 一种草酸艾司西酞普兰口崩片及其制备方法
CN106860410A (zh) * 2017-03-17 2017-06-20 万全万特制药江苏有限公司 一种草酸艾司西酞普兰口崩片及其制备方法
WO2024165628A1 (fr) 2023-02-07 2024-08-15 Kinast Lasse Forme pharmaceutique orale à libération immédiate d'escitalopram ou de racémate de celui-ci avec une teneur accrue en api

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999032092A1 (fr) * 1997-12-19 1999-07-01 Smithkline Beecham Corporation Comprimes a dispersion rapide
US20060134195A1 (en) * 2002-11-25 2006-06-22 Yourong Fu Mannose-based fast dissolving tablets
WO2006092812A2 (fr) * 2005-03-02 2006-09-08 Actavis Group Hf. Forme posologique a desintegration rapide comprenant du carbonate de magnesium lourd
WO2006123243A2 (fr) * 2005-05-20 2006-11-23 Aurobindo Pharma Limited Formes galeniques pharmaceutiques d'un antidepresseur
WO2007050697A2 (fr) * 2005-10-26 2007-05-03 Azur Pharma Iii Limited Compositions et procedes pour l'administration de medicaments psychotropes destines a moduler le poids corporel
EP1813275A1 (fr) * 2005-12-20 2007-08-01 Teva Pharmaceutical Industries Ltd Comprime oral desintegrable de lansoprazole
WO2008046617A1 (fr) * 2006-10-20 2008-04-24 Ratiopharm Gmbh Escitalopram et composition pharmaceutique solide comprenant cette structure

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999032092A1 (fr) * 1997-12-19 1999-07-01 Smithkline Beecham Corporation Comprimes a dispersion rapide
US20060134195A1 (en) * 2002-11-25 2006-06-22 Yourong Fu Mannose-based fast dissolving tablets
WO2006092812A2 (fr) * 2005-03-02 2006-09-08 Actavis Group Hf. Forme posologique a desintegration rapide comprenant du carbonate de magnesium lourd
WO2006123243A2 (fr) * 2005-05-20 2006-11-23 Aurobindo Pharma Limited Formes galeniques pharmaceutiques d'un antidepresseur
WO2007050697A2 (fr) * 2005-10-26 2007-05-03 Azur Pharma Iii Limited Compositions et procedes pour l'administration de medicaments psychotropes destines a moduler le poids corporel
EP1813275A1 (fr) * 2005-12-20 2007-08-01 Teva Pharmaceutical Industries Ltd Comprime oral desintegrable de lansoprazole
WO2008046617A1 (fr) * 2006-10-20 2008-04-24 Ratiopharm Gmbh Escitalopram et composition pharmaceutique solide comprenant cette structure

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20120106A1 (it) * 2012-01-30 2013-07-31 Carthesia S A S Pastiglie liofilizzate di escitalopram ossalato per somministrazione sublinguale
WO2013114416A1 (fr) 2012-01-30 2013-08-08 Carthesia S.A.S. Comprimés lyophilisés d'oxalate d'escitalopram destinés à être administrés par voie sublinguale
WO2014184663A3 (fr) * 2013-05-15 2015-01-22 Apr Applied Pharma Research Sa Formulations de médicaments dispersables par voie orale
CN104523638A (zh) * 2014-11-28 2015-04-22 浙江华海药业股份有限公司 含有草酸艾司西酞普兰的片剂及其制备方法
CN104523638B (zh) * 2014-11-28 2020-02-21 浙江华海药业股份有限公司 含有草酸艾司西酞普兰的片剂及其制备方法
CN106038501A (zh) * 2016-06-30 2016-10-26 北京万全德众医药生物技术有限公司 一种草酸艾司西酞普兰口崩片及其制备方法
CN106860410A (zh) * 2017-03-17 2017-06-20 万全万特制药江苏有限公司 一种草酸艾司西酞普兰口崩片及其制备方法
WO2024165628A1 (fr) 2023-02-07 2024-08-15 Kinast Lasse Forme pharmaceutique orale à libération immédiate d'escitalopram ou de racémate de celui-ci avec une teneur accrue en api

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