WO2013160916A1 - Dispersion solide de malate de sunitinib - Google Patents

Dispersion solide de malate de sunitinib Download PDF

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Publication number
WO2013160916A1
WO2013160916A1 PCT/IN2013/000280 IN2013000280W WO2013160916A1 WO 2013160916 A1 WO2013160916 A1 WO 2013160916A1 IN 2013000280 W IN2013000280 W IN 2013000280W WO 2013160916 A1 WO2013160916 A1 WO 2013160916A1
Authority
WO
WIPO (PCT)
Prior art keywords
sunitinib malate
solid dispersion
pharmaceutically acceptable
amorphous solid
acceptable carrier
Prior art date
Application number
PCT/IN2013/000280
Other languages
English (en)
Inventor
Bandi Parthasaradhi Reddy
Kura Rathnakar Reddy
Dasari Muralidhara Reddy
Thungathurthy Srinivasa Rao
Bandi Vamsi Krishna
Original Assignee
Hetero Research Foundation
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 Hetero Research Foundation filed Critical Hetero Research Foundation
Publication of WO2013160916A1 publication Critical patent/WO2013160916A1/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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol

Definitions

  • the present invention provides a novel amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier, process for its preparation and pharmaceutical compositions comprising it.
  • Polymorphism is defined as "the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice.
  • polymorphs are different crystalline structures of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules.
  • Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph.
  • Solvent medium and mode of crystallization play very important role in obtaining one polymorphic Form over the other.
  • Sunitinib and its malate salt can exist in different polymorphic Forms, which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
  • U.S. patent application publication no. 2003/0069298 disclosed two crystal forms, Form I (characterized by an x-ray powder diffraction patterns having peaks expressed as 20 at 13.2, 19.4, 24.2 and 25.5 degrees) and Form II (characterized by an x-ray powder diffraction patterns having peaks expressed as 20 at 3.0, 12.1 , 14.5 and 27.7 degrees) of sunitinib malate.
  • a novel amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier.
  • the amorphous solid dispersion of sunitinib malate is stable, reproducible and so, the amorphous solid dispersion of sunitinib malate is suitable for formulating sunitinib malate.
  • Normally amorphous Forms are hygroscopic.
  • Amorphous solid dispersion of sunitinib malate is found to be non- hygroscopic.
  • an object of the present invention is to provide amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier, process for its preparation and pharmaceutical compositions comprising it.
  • the present invention there is provided a process for the preparation of amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier, which comprises:
  • compositions comprising a therapeutically effective amount of amorphous solid dispersion of sunitinib malate along with a pharmaceutically acceptable carrier, and at least one pharmaceutically acceptable excipient.
  • Figure 1 is a powder X-ray diffractogram patterns of amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier.
  • Powder X-ray diffraction spectrum was measured on a bruker AXS D8 advance powder X-ray diffractometer having a copper- ⁇ radiation. Approximately 500 mg of sample was gently flattered on a sample holder and scanned from 2 to 50 degrees two- theta, at 0.020 degrees two theta per step and a step time of 1 second. The sample was simply placed on the sample holder. The sample was rotated at 30 rpm at a voltage 40 kV and current 35 mA.
  • room temperature refers to temperature at about 25 to 35°C.
  • amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier there is provided amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carriers may be one or more of copovidone, span 20, ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol or soluplus.
  • a process for the preparation of amorphous solid dispersion of sunitinib malate in combination with a pharmaceutically acceptable carrier which comprises:
  • Sunitinib malate used in step (a) may preferably be sunitinib malate obtained by the known process.
  • the pharmaceutically acceptable carriers used in step (a) may be selected form copovidone or hydroxypropyl methylcellulose.
  • Freeze drying refers to a sublimation process that removes free water or other solvent in the form of solid.
  • the present invention provides a pharmaceutical composition containing said solid dispersion along with the pharmaceutically acceptable excipients such as diluents, chelating agents, disintegrant, glidant, binders, surfactants, coloring agents and/or luricants.
  • pharmaceutically acceptable excipients such as diluents, chelating agents, disintegrant, glidant, binders, surfactants, coloring agents and/or luricants.
  • diluents include calcium carbonate, calcium phosphate- dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol, sorbitol, starch, starch pregelatinized, sucrose, sugar compressible, sugar confectioners, and the like and mixtures thereof.
  • Surfactants include both non-ionic and ionic (cationic, anionic and zwitterionic) surfactants suitable for use in pharmaceutical dosage forms. These include polyethoxylated fatty acids and its derivatives, for example, polyethylene glycol 400 distearate, polyethylene glycol-20 dioleate, polyethylene glycol 4 - 150 mono dilaurate, and polyethylene glycol - 20 glyceryl stearate; alcohol - oil transesterification products, for example, polyethylene glycol - 6 corn oil; polyglycerized fatty acids, for example, polyglyceryl - 6 pentaoleate; propylene glycol fatty acid esters, for example, propylene glycol monocaprylate; mono and diglycerides, for example, glyceryl ricinoleate; sterol and sterol derivatives; sorbitan fatty acid esters and its derivatives, for example, polyethylene glycol - 20 sorbitan monooleate and sorbitan monol
  • L-HPC sodium starch glycollate, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, croscarmellose sodium A-type (Ac-di-sol), starch, crystalline cellulose, hydroxypropyl starch, pregelatinized starch, and the like and mixtures thereof.
  • lubricants/glidants include colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax, and the like and mixtures thereof.
  • Coloring agents include any FDA approved colors for oral use.
  • a mixture of sunitinib malate (50 gm) and hydroxypropyl methylcellulose (75 gm) was dissolved in water (500 ml) at room temperature. The contents were then heated to 70 to 80°C and stirred for 30 minutes to obtain a clear solution. The solution was then cooled to room temperature and filtered. The resulting filtrate was subjected to freeze drying at room temperature for 42 hours to obtain 1 15 gm of amorphous sunitinib malate solid dispersion with hydroxypropyl methylcellulose.
  • a mixture of sunitinib malate (25 gm) and soluplus (50 gm) was dissolved in water (400 ml) at room temperature. The contents were then heated to 70 to 80°C and stirred for 30 minutes to obtain a clear solution. The solution was then cooled to room temperature and filtered. The resulting filtrate was subjected to freeze drying at room temperature for 40 hours to obtain 60 gm of amorphous sunitinib malate solid dispersion with soluplus.

Abstract

La présente invention concerne une nouvelle dispersion solide amorphe de malate de sunitinib en combinaison avec un excipient pharmaceutiquement acceptable, son procédé de préparation, et des compositions pharmaceutiques la comprenant. Selon un aspect, la présente invention porte sur une dispersion solide amorphe de malate de sunitinib en combinaison avec un excipient pharmaceutiquement acceptable. Selon un autre aspect, la présente invention porte sur un procédé de préparation de la dispersion solide amorphe de malate de sunitinib en combinaison avec un excipient pharmaceutiquement acceptable, lequel procédé de préparation consiste à: a) préparer une solution comprenant un mélange de malate de sunitinib et un ou plusieurs excipients pharmaceutiquement acceptables sélectionnés parmi la copovidone, le span 20, l'éthyl cellulose, l'hydroxypropyl méthylcellulose, le polyéthylène glycol ou le soluplus dans de l'eau; et b) soumettre la solution résultante à une lyophilisation pour obtenir la dispersion solide amorphe de malate de sunitinib en combinaison avec un excipient pharmaceutiquement acceptable.
PCT/IN2013/000280 2012-04-25 2013-04-25 Dispersion solide de malate de sunitinib WO2013160916A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1631/CHE/2012 2012-04-25
IN1631CH2012 2012-04-25

Publications (1)

Publication Number Publication Date
WO2013160916A1 true WO2013160916A1 (fr) 2013-10-31

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Application Number Title Priority Date Filing Date
PCT/IN2013/000280 WO2013160916A1 (fr) 2012-04-25 2013-04-25 Dispersion solide de malate de sunitinib

Country Status (1)

Country Link
WO (1) WO2013160916A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106974890A (zh) * 2016-01-15 2017-07-25 常州方楠医药技术有限公司 一种无定型舒尼替尼l-苹果酸盐与药用辅料的固体分散体及其制备方法
US10183020B2 (en) 2014-01-02 2019-01-22 Astrazeneca Ab Pharmaceutical compositions comprising AZD9291
WO2020101596A3 (fr) * 2018-08-10 2020-07-09 Arven Ilac Sanayi Ve Ticaret Anonim Sirketi Composition de capsule comprenant du sunitinib
WO2020216450A1 (fr) 2019-04-25 2020-10-29 Synthon B.V. Composition pharmaceutique comprenant du sunitinib amorphe
US20210220286A1 (en) * 2018-04-26 2021-07-22 Synthon B.V. Pharmaceutical composition comprising amorphous sunitinib
WO2024039213A1 (fr) * 2022-08-19 2024-02-22 주식회사 스카이테라퓨틱스 Sunitinib amorphe, son procédé de production et composition pharmaceutique le comprenant

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009111623A2 (fr) * 2008-03-06 2009-09-11 Dr. Reddy's Laboratories Ltd. Tartrate de varénicline amorphe
WO2009156837A2 (fr) * 2008-06-26 2009-12-30 Medichem, S.A. Forme amorphe d'un sel de malate de 2-indolinone à substitution 3-pyrrole

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009111623A2 (fr) * 2008-03-06 2009-09-11 Dr. Reddy's Laboratories Ltd. Tartrate de varénicline amorphe
WO2009156837A2 (fr) * 2008-06-26 2009-12-30 Medichem, S.A. Forme amorphe d'un sel de malate de 2-indolinone à substitution 3-pyrrole

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BENJAKUL ET AL.: "Preparation of Dry Reconstituted Liposomal Powder by Freeze-Drying at Room Temperature..", JOUMAL OF LIPOSOME RESEARCH, vol. 21, no. 1, 2011, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.govlpubmed/20387991> [retrieved on 20130805] *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10183020B2 (en) 2014-01-02 2019-01-22 Astrazeneca Ab Pharmaceutical compositions comprising AZD9291
CN106974890A (zh) * 2016-01-15 2017-07-25 常州方楠医药技术有限公司 一种无定型舒尼替尼l-苹果酸盐与药用辅料的固体分散体及其制备方法
US20210220286A1 (en) * 2018-04-26 2021-07-22 Synthon B.V. Pharmaceutical composition comprising amorphous sunitinib
WO2020101596A3 (fr) * 2018-08-10 2020-07-09 Arven Ilac Sanayi Ve Ticaret Anonim Sirketi Composition de capsule comprenant du sunitinib
WO2020216450A1 (fr) 2019-04-25 2020-10-29 Synthon B.V. Composition pharmaceutique comprenant du sunitinib amorphe
WO2024039213A1 (fr) * 2022-08-19 2024-02-22 주식회사 스카이테라퓨틱스 Sunitinib amorphe, son procédé de production et composition pharmaceutique le comprenant

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