Solid dispersions containing an apoptosis-inducing agent

Abstract

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, 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

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of provisional application Ser. No. 61 / 408,517, filed Oct. 29, 2010, which is hereby incorporated by reference as if set forth in its entirety.[0002]Cross-reference is also made, without claim to benefit of priority or admission as to prior art status, to the following pending U.S. application containing subject matter related to the present application: Ser. No. 12 / 787,682 (U.S. 2010 / 0305122) titled “Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases,” the entire disclosure of which is incorporated herein by reference.FIELD OF THE INVENTION[0003]The present invention relates to solid dispersions comprising an apoptosis-inducing agent, to pharmaceutical dosage forms comprising such dispersions, to processes for preparing such dispersions and dosage forms and to methods of use thereof for treating diseases characterized by overexpression of anti-apoptotic Bcl-2 famil...

AI Technical Summary

Benefits of technology

[0023]Apoptosis-inducing drugs that target Bcl-2 family proteins such as Bcl-2 and Bcl-XL are best administered according to a regimen that provides continual, for example daily, replenishment of the plasma concentration, to maintain the concentration in a therapeutically effective range. This can be achieved by daily parenteral, e.g., intravenous (i.v.) or intraperitoneal (i.p.) administration. However, daily parenteral administration is often not practical in a clinical se...

Problems solved by technology

Currently, there is not an approved treatment regimen that produces a cure, and current guidelines recommend that patients be treated in the context of a clinical trial, even in a first-line setting.

Most lymphomas respond initially to any one of these therapies, but tumors typically recur and eventually become refractory.

However, many tumors ultimately become resistant to these agents.

Where aqueous solubility of Bcl-2 binding compounds is very low, the formulator faces a significant challenge in assuring acceptable oral bioavailability, which is strongly dependent on solubility in the aqueous medium o...

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