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WO2012014012A1 - Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie - Google Patents

Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie Download PDF

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Publication number
WO2012014012A1
WO2012014012A1 PCT/IB2010/053405 IB2010053405W WO2012014012A1 WO 2012014012 A1 WO2012014012 A1 WO 2012014012A1 IB 2010053405 W IB2010053405 W IB 2010053405W WO 2012014012 A1 WO2012014012 A1 WO 2012014012A1
Authority
WO
WIPO (PCT)
Prior art keywords
weight
olanzapine
ingredients
tablets
procedure
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IB2010/053405
Other languages
English (en)
Spanish (es)
Inventor
Andrés RUDOLPHY FONTAINE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Laboratorios Andromaco SA
Original Assignee
Laboratorios Andromaco SA
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=45529468&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2012014012(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Laboratorios Andromaco SA filed Critical Laboratorios Andromaco SA
Priority to PCT/IB2010/053405 priority Critical patent/WO2012014012A1/fr
Priority to PE2010000482A priority patent/PE20120216A1/es
Publication of WO2012014012A1 publication Critical patent/WO2012014012A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K31/55—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
    • A61K9/0012—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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Definitions

  • the present invention is related to a process for preparing a pharmaceutical fast-dissolving oral composition in the form of tablets comprising olanzapine form I.
  • Olanzapine is an antipsychotic agent, used for the treatment of schizophrenia. It was described in US Patent 5,229,382, subsequently several crystalline modifications of olanzapine were revealed, which includes some hydrated or solvated forms that are stable in ambient condition.
  • compositions containing olanzapine such as those described in US patents US 5,229,382, US 5,919,485 and EP0733367, which lead to the obtaining of various pharmaceutical forms, such as tablets, capsules, lyophilized powder for reconstitution in aqueous solvent, controlled release injection for intramuscular application.
  • Patent EP0733367B1 describes a solid oral composition comprising olanzapine as an active ingredient, preferably olanzapine form II, intimately mixed with a filler, a binder, a disintegrant, a dry binder to provide adequate friability, and a lubricant, wherein said formulation is coated with a polymer.
  • the coating with certain polymers aims to provide uniformity and physical stability, in addition to effectively preventing the phenomenon of undesirable color change from the formulation. It is mentioned that olanzapine tends to be metastable, to undergo pharmaceutically unwanted color change and requires treatments to ensure the homogeneity of the final solid formulation. The color change may occur when it comes into contact with certain excipients that include powder mixtures.
  • olanzapine used by these inventors corresponds to the anhydrous form which, as indicated by them, is the most stable form of olanzapine. Even so it is noted that this olanzapine may form an undesirable crystalline form in the presence of certain solvents or excipients.
  • the inventors of the EP0733367 patent believe that a direct compression process of the dry mix or dry granulated processes to prepare the solid oral formulations, are procedures that will create a greater risk of poor dose uniformity. Due to the potent nature of olanzapine, a constant dose uniformity is necessary.
  • patent EP0733367 comprises the stages of wet granulation, drying, mixing with additional excipients and compression.
  • the inventors have discovered and so describe it in the European patent, that an aqueous wet granulation with high shear with fluid bed drying, is the most effective method for preparing pharmaceutically stable oral olanzapine formulations.
  • EP1558219 describes a process for preparing tablets by direct compression of a mixture of the components without the addition of a solvent. It is mentioned that with this procedure it was possible to obtain stable tablets and that have dose uniformity, unlike expected by the background described regarding the instability of olanzapine. For this it was necessary to select certain excipients and exclude others. Thus they describe a formulation with two elementary ingredients that are a monosaccharide and / or oligosaccharide and a polysaccharide in a total concentration of 70 to 90%. It is indicated that the oligosaccharide should not be microcrystalline cellulose because of its hygroscopic characteristics, which decreases the stability of olanzapine.
  • Rapid oral dissolution tablets are an excellent pharmaceutical form to administer to patients with psychosis or other mental disorders that require olanzapine in their treatment, since water intake is avoided, an additional problem in the administration of medications to these patients .
  • Quick dissolving tablets dissolve in saliva immediately after being administered, so the medication can be ingested without the need for water supply.
  • crospovidone is used as a superdisintegrant, in concentrations equal to or less than 3%.
  • oral rapid dissolution tablets refers to tablets that are dispersed in water within 30 seconds, preferably within 10 seconds and more preferably within 5 seconds or less, as specified in the Pharmacopoeia of United States for a rapid dissolution dosage form.
  • Form I of olanzapine has an X-ray powder diffraction pattern as indicated below, where d represents the interplanar space.
  • a Siemens 5000 X-ray diffractometer was used.
  • Table 1 - X-ray powder diffraction pattern of olanzapine form I used in the present invention.
  • the process of the present invention consists of the following steps, where each of the percentages of the indicated ingredients is expressed with respect to the total weight of the pharmaceutical composition or final product: a) Sift by granulator in C-0.7 mesh the following Ingredients in the order indicated:
  • Olanzapine form I (2.0% to 8.0%)
  • Crospovidone (2.5% to 3.0%)
  • Lactose spried dried monohydrate (8.0% to 10.0%)
  • Microcrystalline cellulose 24.0% to 26.0%
  • Manually sift in mesh No. 60 the following ingredients, adding a portion of the previous mixture:
  • Dye 10 D&C yellow 10 u Red iron oxide (0.5% to 0.8%)
  • oral fast dissolving tablets comprising the ingredients listed in Table 2 at the indicated concentrations, which are expressed in% by weight with respect to the total weight of the compressed. Table 2.- Ingredients of the oral fast dissolving tablets obtained with the procedure of Example 1.
  • the oral fast-dissolving tablets obtained according to the composition described in Example 2 were stored since their elaboration in their final containers, in the condition of 40 ⁇ ⁇ 2 ⁇ C and 75% ⁇ 5% relative humidity (CONDITION 1) and in ambient condition of 30 ° C ⁇ 2 ⁇ C and 65% ⁇ 5% relative humidity (CONDITION 2). Samples were taken at time zero (T0), at 30 days (T30), at 60 days (T60), at 90 days (T90) and at 180 days (T180), and the corresponding analyzes were performed.
  • CONDITION 1 • Samples: 10.0 mg / tablet with a range of 93.5% to 102.0%, CV: 1, 86%.

Landscapes

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

Abstract

La présente invention concerne un procédé pour préparer un comprimé à dissolution rapide orale qui comprend en tant qu'unique principe actif la forme I d'olanzapine. Le procédé comprend les étapes suivantes consécutives qui consistent : a) à tamiser à l'aide d'un moulin le principe actif avec trois excipients à savoir des diluants et un superdésintégrant; b) à tamiser manuellement de manière séparée deux autres excipients à savoir un colorant et un lubrifiant, et à mélanger avec les ingrédients de l'étape précédente; c) à tamiser par granulateur trois autres excipients à savoir un édulcorant, de l'essence et un diluant, à incorporer les ingrédients de l'étape précédente et à mélanger; d) à tamiser manuellement deux autres excipients à savoir un lubrifiant et un glissant, à mélanger à tous les ingrédients des étapes précédentes; et e) à mettre en oeuvre le procédé de compression directe pour former des comprimés à dissolution rapide orale qui contiennent 2,0 % à 8,0 % de la forme I d'olanzapine; 44,0 % à 48,0 % de manitol en poudre; 24,0 % à 26,0 % de cellulose microcristalline; 8,0 % à 10,0 % de monohydrate de lactose desséché par pulvérisation; 2,5 % à 3,0 % de crospovidone; 0,5 % à 0,8 % de colorant; 4,0 % à 6,0 % d'essence; 0,8 % à 1,2 % de sucralose en poudre; 3,2 % à 4,8 % de talc; 0,8 % à 1,0 % de dioxyde de silicium colloïdal et 0,8 % à 1,0 % de stéarate de magnésium; tous les pourcentages étant exprimés en poids par rapport au poids total du comprimé. L'invention concerne également une composition pharmaceutique, sous forme de comprimés à dissolution rapide orale obtenus par ce procédé et leur utilisation pour le traitement de la schizophrénie.
PCT/IB2010/053405 2010-07-27 2010-07-27 Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie Ceased WO2012014012A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/IB2010/053405 WO2012014012A1 (fr) 2010-07-27 2010-07-27 Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie
PE2010000482A PE20120216A1 (es) 2010-07-27 2010-08-02 Procedimiento para preparar comprimidos de disolucion rapida oral que comprenden la forma i de olanzapina y los comprimidos obtenidos

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2010/053405 WO2012014012A1 (fr) 2010-07-27 2010-07-27 Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie

Publications (1)

Publication Number Publication Date
WO2012014012A1 true WO2012014012A1 (fr) 2012-02-02

Family

ID=45529468

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2010/053405 Ceased WO2012014012A1 (fr) 2010-07-27 2010-07-27 Procédé pour préparer des comprimés à dissolution rapide orale qui comprennent la forme i d'olanzapine, comprimés obtenus et leur utilisation pour le traitement de la schizophrénie

Country Status (2)

Country Link
PE (1) PE20120216A1 (fr)
WO (1) WO2012014012A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004035027A1 (fr) * 2002-10-18 2004-04-29 Krka, Tovarna Zdravil, D.D., Novo Mesto Formulation pharmaceutique d'olanzapine
EP1681048A1 (fr) * 2005-01-14 2006-07-19 Krka Tovarna Zdravil, D.D., Novo Mesto Composition à désintégration orale à base d'olanzépine ou de donepézil
WO2006081779A2 (fr) * 2005-02-02 2006-08-10 Zentiva, A.S. Preparation pharmaceutique contenant de l'olanzapine en tant que principe actif et son procede de preparation
ES2279715A1 (es) * 2005-12-26 2007-08-16 Laboratorios Lesvi, S.L. Formulacion oral de olanzapina.
WO2008037502A2 (fr) * 2006-09-29 2008-04-03 Synthon B.V. Composition pharmaceutique d'olanzapine
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004035027A1 (fr) * 2002-10-18 2004-04-29 Krka, Tovarna Zdravil, D.D., Novo Mesto Formulation pharmaceutique d'olanzapine
EP1681048A1 (fr) * 2005-01-14 2006-07-19 Krka Tovarna Zdravil, D.D., Novo Mesto Composition à désintégration orale à base d'olanzépine ou de donepézil
WO2006081779A2 (fr) * 2005-02-02 2006-08-10 Zentiva, A.S. Preparation pharmaceutique contenant de l'olanzapine en tant que principe actif et son procede de preparation
ES2279715A1 (es) * 2005-12-26 2007-08-16 Laboratorios Lesvi, S.L. Formulacion oral de olanzapina.
WO2008037502A2 (fr) * 2006-09-29 2008-04-03 Synthon B.V. Composition pharmaceutique d'olanzapine
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles

Also Published As

Publication number Publication date
PE20120216A1 (es) 2012-03-23

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