WO2013172805A1 - Formulations de nouveaux comprimés orodispersibles d'olanzapine - Google Patents

Formulations de nouveaux comprimés orodispersibles d'olanzapine Download PDF

Info

Publication number
WO2013172805A1
WO2013172805A1 PCT/TR2013/000149 TR2013000149W WO2013172805A1 WO 2013172805 A1 WO2013172805 A1 WO 2013172805A1 TR 2013000149 W TR2013000149 W TR 2013000149W WO 2013172805 A1 WO2013172805 A1 WO 2013172805A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
range
formulation according
binder
olanzapine
Prior art date
Application number
PCT/TR2013/000149
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2013172805A1 publication Critical patent/WO2013172805A1/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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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 is related to pharmaceutical formulations comprising olanzapine used in the treatment of schizophrenia group of psychotic disorders, to provide clinical improvement in maintenance treatment of patients who respond to the first-line treatment, in bipolar disorder, in the treatment of heavy and moderate manic periods and to prevent their recurrence.
  • Said formulations are characterized in being in orodispersible tablet form.
  • the molecule olanzapine which is shown with Formula I was first disclosed in the patent numbered EP045436. It was also disclosed in said document that the molecule is a potential neuroleptic having anxiolytic, relaxing, antiemetic properties; it is useful in treatment of psychotic cases such as schizophrenia, schizophrenia group disorders and acute mania; it is used in low doses in treatment of mild cases of anxiety.
  • Olanzapine is in 2.5, 5, 7.5, 10, 15, 20 mg film tablet; 5, 10, 15, 20 mg orodispersible tablet; 2.5, 5, 10, 15, 20 mg tablet and 5, 10 mg bisect film tablet forms on the market.
  • Dissolution and dispersion time of tablets obtained from pharmaceutical formulations formulated in orodispersible tablet form and comprising olanzapine in mouth when taken orally are quite important on absorption of olanzapine into the blood and its bioavailability.
  • olanzapine is a non-water-soluble molecule. Therefore it is significant that the mechanical properties of the tablet forms obtained are at optimum levels during preparation of formulations comprising olanzapine in order for said tablet forms to dissolve easily and disperse fast.
  • the tablets obtained from the orodispersible formulations comprising olanzapine do not have optimum tablet hardness and brittleness values, the tablets do not disperse in the mouth easily or break into small pieces fast.
  • the orodispersible tablet formulations of olanzapine which comprise at least one low-density cellulose derivative as the binder have the required hardness and brittleness values and therefore provide an effective treatment by realizing the required active agent bioavailability as they can disperse easily and fast in the mouth.
  • the first element of the present invention is orodispersible tablet formulations of olanzapine which comprise at least one low-density cellulose derivative as the binder.
  • the present invention is related to orodispersible tablet formulations of olanzapine which comprise at least one low-density cellulose derivative as the binder.
  • said orodispersible tablet formulation comprises the active agent olanzapine in the range of 0.1-25%, preferably in the range of 0.5-20%, more preferably in the range of 1-15%.
  • the subject of the present invention is that said formulation comprises the active agent olanzapine in the range of 0.05-15 mg, preferably in the range of 0.1 -12 mg, more preferably in the range of 1-10 mg.
  • the active agent olanzapine used in the formulations of the present invention can be in the form of its solvates, hydrates, esters, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or a combination thereof.
  • the formulation comprises a low-density cellulose derivative in the range of 0.5-25%, preferably in the range of 2-20%, more preferably in the range of 5-15% as the binder.
  • the low-density cellulose derivative that is used as the binder in the formulation of the present invention can be selected from a group comprising hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, ethyl methyl cellulose, hydroxy ethyl cellulose, hydroxy ethyl methyl cellulose, ethyl hydroxy ethyl cellulose and carboxymethyl cellulose and/or combinations thereof.
  • the low-density cellulose derivative that is used as the binder in the formulation of the present invention can preferably be low-density hydroxy propyl cellulose.
  • hydroxy propyl cellulose comprises hydroxy propoxyl group in the range of 1-30%, preferably in the range of 2-25%, more preferably in the range of 5-20%.
  • a characteristic feature of the formulation of the present invention is that hydroxy propyl cellulose used as the binder comprises hydroxy propoxyl group in the range of 1-30%, preferably in the range of 2-25%, more preferably in the range of 5-20%.
  • Dispersion characteristics of the orodispersible tablets comprising olanzapine are affected by particle size of the binder as well as selection of the binder.
  • the inventors focused particularly on low-density hydroxypropyl cellulose and have observed that the tablets present optimum dispersion characteristics in the case that the particle size of this binder is in the range of 5-85 ⁇ , preferably in the range of 10-80 ⁇ , more preferably in the range of 20-70 ⁇ .
  • the particle size of low-density hydroxy propyl cellulose used as binder in the formulation is in the range of 5-85 ⁇ , preferably in the range of 10-80 ⁇ , more preferably in the range of 20-70 ⁇ .
  • the formulation comprises at least one pharmaceutically acceptable excipient in addition to olanzapine used as the active agent and low-density cellulose derivative substance.
  • excipients that can be used in the formulation prepared according to the invention can be selected from a group comprising diluent, sweetener, flavouring agent and lubricant or combinations thereof.
  • said formulation comprises at least one diluent in the range of 20-99%, preferably in the range of 30-95%, more preferably in the range of 40-90%.
  • the diluent in the formulations of the present invention can be selected from a group comprising microcrystalline cellulose, lactose, sorbitol, silicon dioxide, dicalcium phosphate or a combination thereof.
  • lactose more preferably lactose monohydrate can be used as the diluent in the formulations of the present invention.
  • the sweetener in the formulations of the present invention can be selected from a group comprising acesulfame, aspartame, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose.
  • the flavouring agent in the formulations of the present invention can be selected from a group comprising levomenthol, menthane, anethole, methyl salicylate, eucalyptol, cinnamon, 1- methyl acetate, sage, eugenol, oxanone, lemon, orange, strawberry, blackberry or combinations thereof.
  • the lubricant in the formulations of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
  • the formulations prepared according to the present invention can comprise olanzapine in the range of 0.1 -25%, diluent in the range of 20-99%, binder in the range of 0.5-25%, sweetener in the range of 0.1-5%, flavoring agent in the range of 0.1-2.5% and lubricant in the range of 0.1-5% in proportion to total weight of unit dose.
  • olanzapine is mixed with the diluent and the binder.
  • the mixture granulated with a granulation solution comprising diluent is dried and sieved.
  • the sweetener and the flavoring agent are added to the mixture.
  • the mixture is lubricated with the lubricant and sent to tablet compression.
  • the formulation of the present invention can be used in the treatment of schizophrenia group of psychotic disorders, to provide clinical improvement in maintenance treatment of patients who respond to the first-line treatment, in bipolar disorder, in the treatment of heavy and moderate manic periods and to prevent their recurrence.
  • the formulation given above is prepared by wet granulation method. Olanzapine is mixed with the diluent and the binder. The mixture granulated with the granulation solution comprising diluent is dried and sieved. The sweetener and the flavoring agent are added to the mixture. Lastly, the mixture is lubricated with the lubricant and sent to tablet compression.

Abstract

La présente invention a pour objet des formulations pharmaceutiques comprenant l'olanzapine utilisées dans le traitement du groupe de type schizophrénie de troubles psychotiques, pour offrir une amélioration clinique dans le traitement d'entretien des patients qui répondent au traitement de première intention, dans le trouble bipolaire, dans le traitement de périodes maniaques lourdes et modérées et pour prévenir leur récurrence. Lesdites formulations sont caractérisées en ce qu'elles sont sous forme de comprimé orodispersible.
PCT/TR2013/000149 2012-05-14 2013-05-08 Formulations de nouveaux comprimés orodispersibles d'olanzapine WO2013172805A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2012/05570 2012-05-14
TR201205570 2012-05-14

Publications (1)

Publication Number Publication Date
WO2013172805A1 true WO2013172805A1 (fr) 2013-11-21

Family

ID=48783323

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2013/000149 WO2013172805A1 (fr) 2012-05-14 2013-05-08 Formulations de nouveaux comprimés orodispersibles d'olanzapine

Country Status (1)

Country Link
WO (1) WO2013172805A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111603506A (zh) * 2020-07-01 2020-09-01 上海市精神卫生中心（上海市心理咨询培训中心） 调胃承气汤在制备防治精神分裂症患者服用奥氮平引起的代谢综合症的药物中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0045436A1 (fr) 1980-08-04 1982-02-10 International Business Machines Corporation Dispositif à aspiration pour l'alimentation en documents
WO2006092812A2 (fr) * 2005-03-02 2006-09-08 Actavis Group Hf. Forme posologique a desintegration rapide comprenant du carbonate de magnesium lourd
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles
EP2246046A1 (fr) * 2009-04-28 2010-11-03 Sanovel Ilac Sanayi ve Ticaret A.S. Comprimé d'olanzapine à désintégration orale
KR20110056071A (ko) * 2009-11-20 2011-05-26 고려제약주식회사 올란자핀을 함유하는 확산정 조성물 및 이에 의해 형성된 정제

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0045436A1 (fr) 1980-08-04 1982-02-10 International Business Machines Corporation Dispositif à aspiration pour l'alimentation en documents
WO2006092812A2 (fr) * 2005-03-02 2006-09-08 Actavis Group Hf. Forme posologique a desintegration rapide comprenant du carbonate de magnesium lourd
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles
EP2246046A1 (fr) * 2009-04-28 2010-11-03 Sanovel Ilac Sanayi ve Ticaret A.S. Comprimé d'olanzapine à désintégration orale
KR20110056071A (ko) * 2009-11-20 2011-05-26 고려제약주식회사 올란자핀을 함유하는 확산정 조성물 및 이에 의해 형성된 정제

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DIVATE S ET AL: "Fast disintegrating tablets - An emerging trend", INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES REVIEW AND RESEARCH 2011 GLOBAL RESEARCH ONLINE IND, vol. 6, no. 2, January 2011 (2011-01-01), pages 18 - 22, XP002707392, ISSN: 0976-044X *
MATSUOKA M ET AL: "Pharmaceutical composition used as orally disintegrating tablet contains irbesartan, and binder such as hydroxypropyl cellulose and/or polyvinyl alcohol", WPI / THOMSON,, vol. 2010, no. 23, 11 March 2010 (2010-03-11), XP002669870 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111603506A (zh) * 2020-07-01 2020-09-01 上海市精神卫生中心（上海市心理咨询培训中心） 调胃承气汤在制备防治精神分裂症患者服用奥氮平引起的代谢综合症的药物中的应用

Similar Documents

Publication Publication Date Title
US20210228489A1 (en) Compositions for treating cystic fibrosis
RU2446800C2 (ru) Препаративные формы с контролируемым высвобождением
US9597291B2 (en) Orally disintegrating tablet containing asenapine
EP2749270B1 (fr) Racécadotril et ses compositions pharmaceutiques
JP7425603B2 (ja) 医薬組成物
US20200146977A1 (en) Pharmaceutical Composition for Oral Administration Comprising Enzalutamide
Preethi et al. Formulation of fast-dissolving tablets of doxazosin mesylate drug by direct compression method
US20160120870A1 (en) The process for the preparation of a pharmaceutical composition comprising rivaroxaban
WO2011139252A2 (fr) Formulations effervescentes comprenant du cefdinir
WO2021108343A1 (fr) Formulations comprenant des médicaments abaissant les lipides et abaissant la pression sanguine
CA2972234C (fr) Formulation pharmaceutique renfermant un aprepitant
WO2013172805A1 (fr) Formulations de nouveaux comprimés orodispersibles d'olanzapine
PT1944028E (pt) Formas orais sólidas de ebastina
EP2243468A1 (fr) Compositions comprenant de la diméboline et se désintégrant oralement
WO2011129792A1 (fr) Formulations dispersibles dans l'eau comprenant le cefpodoxime proxétil
WO2013109223A1 (fr) Formulations de particules de tadalafil sous forme effervescente
WO2013100878A1 (fr) Formulations pharmaceutiques comprenant de l'aripiprazole
EP2709596A1 (fr) Préparations effervescentes contenant du dexkétoprofène
JP2010111630A (ja) アズレンスルホン酸塩含有粒子及びその製造方法、ならびにこれを含む医薬製剤
KR20210052495A (ko) 경구 투여용 의약 조성물
PT2082735E (pt) Aripripazole amorfo e processo para a sua preparação
WO2013109230A1 (fr) Compositions pharmaceutiques contenant du tadalafil
WO2014007775A1 (fr) Nouvelle formulation à dissolution rapide
WO2013100871A1 (fr) Formulations effervescentes de rivastigmine
WO2012093971A2 (fr) Compositions effervescentes contenant de l'amlodipine

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: 13736673

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13736673

Country of ref document: EP

Kind code of ref document: A1