Solid dispersions containing an apoptosis-promoting agent

A technology of solid dispersion and solid matrix, which can be used in medical preparations containing active ingredients, organic active ingredients, oil/fat/wax non-active ingredients, etc., and can solve problems such as impracticality

Inactive Publication Date: 2012-11-28
ABBVIE INC
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, daily parenteral administration is often not practical in a clinical setting, especially for outpatients

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Solid dispersions containing an apoptosis-promoting agent
  • Solid dispersions containing an apoptosis-promoting agent
  • Solid dispersions containing an apoptosis-promoting agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0217] Embodiment 1: Preparation of the solid dispersion of ABT-263 diHCl

[0218] ABT-263 diHCl crystalline salt was mixed with surfactant and water-soluble polymer in the following weight ratio:

[0219] 10.8% ABT-263 salt (10% free base equivalent); 10% surfactant; 79.2% polymer

[0220] 21.5% ABT-263 salt (20% free base equivalent); 10% surfactant; 68.5% polymer

[0221] 32.3% ABT-263 salt (30% free base equivalent); 10% surfactant; 57.7% polymer

[0222] 43% ABT-263 salt (40% free base equivalent); 10% surfactant; 47% polymer

[0223] Surfactants in different series are TPGS, Span™ 20 or Tween™ 20. The polymers in different series are copovidone (Kollidon® VA 64), povidone K-30 or HPMC-AS.

[0224] The ingredient mixture was dissolved in methanol in each case. Methanol was removed in vacuo at 65°C using a Genevac® system, and the resulting solid dispersion was allowed to cool to ambient temperature.

[0225] The solid dispersion in each case was sieved through a 4...

Embodiment 2

[0228] Embodiment 2: Preparation of solid dispersion of ABT-263 free base

[0229] ABT-263 diHCl crystalline salt was dissolved in acetone, and NaOH was added to convert ABT-263 diHCl to free base. The NaCl by-product was precipitated and removed by filtration.

[0230] In the acetone solution of obtained ABT-263 free base, add surfactant and water-soluble polymer of following weight ratio:

[0231] 10% ABT-263 free base; 10% surfactant; 80% polymer

[0232] 20% ABT-263 free base; 10% surfactant; 70% polymer

[0233] 30% ABT-263 free base; 10% surfactant; 60% polymer

[0234] 40% ABT-263 free base; 10% surfactant; 50% polymer

[0235] Surfactants in different series are TPGS, Span™ 20 or Tween™ 20. Polymers in different series are copovidone (Kollidon® VA 64) or HPMC-AS.

[0236] Acetone was removed in vacuo at 65°C using a Genevac® system, and the resulting solid dispersion was allowed to cool to ambient temperature.

[0237] The solid dispersion in each case was sie...

Embodiment 3

[0240] Example 3: Dissolution Profile of Solid Dispersions

[0241]Representative dissolution (drug release) profiles in pH 6.5 buffered media containing 7.6 mM Tween® 80 are shown in figure 1 (ABT-263 diHCl) and figure 2 (ABT-263 free base).

[0242] like figure 1 As shown in , at 20% drug loading level, ABT-263 diHCl solid dispersion with 68.5% copovidone and 10% TPGS showed a moderate rate of drug release, which reached a plateau at about 80% release. The release from similar dispersions with Span™ 20 or especially Tween™ 20 as surfactant was much slower.

[0243] In contrast, if figure 2 ABT-263 free base solid dispersion with 70% copovidone and 10% Tween® 20 or TPGS showed fast drug release at the same 20% drug loading level as shown in . In the case of the free base dispersion, only Span™ 20 surfactant resulted in a much slower release.

[0244] The release rate was drug load dependent for both ABT-263 diHCl and free base dispersion formulations, with the 20%...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound, e.g., ABT-263, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

Description

[0001] This application claims the benefit of priority to US Provisional Application Serial No. 61 / 185,105, filed June 8, 2009. [0002] Cross-references were made to the following co-filed U.S. application containing subject matter related to the present application: Serial No. 12 / 796,000 filed June 8, 2010, entitled "Inhibitors for Oral Administration of Bcl-2 Family Inhibitors" Pharmaceutical dosage form for oral administration of a Bcl-2 family inhibitor," which claims the benefit of priority of U.S. Provisional Application Serial No. 61 / 185,130, filed June 8, 2009. [0003] The entire disclosures of each of the above applications are incorporated herein by reference. field of invention [0004] The present invention relates to solid dispersions containing apoptosis-promoting agents, pharmaceutical dosage forms comprising such dispersions, methods for the preparation of such dispersions and dosage forms and their use for the treatment of hyperlipidemia characterized by ant...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K31/5377A61K9/14
CPCA61K9/145A61K9/1652A61K31/495A61K47/38A61K9/4866A61K9/146A61K9/4858A61K9/19A61K47/26A61K9/2027A61K47/32A61K9/1635A61K9/2054A61K47/44A61K47/10A61K47/22A61P1/02A61P1/04A61P1/16A61P1/18A61P11/00A61P13/02A61P13/08A61P13/10A61P13/12A61P15/00A61P17/00A61P19/00A61P21/00A61P25/00A61P27/02A61P35/00A61P35/02A61P43/00A61P5/00
Inventor E.A.施米特童平K.希姆斯特拉C.M.费希尔吴淮亮J.M.米勒Y.李J.S.拉丰泰恩
Owner ABBVIE INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap