abstract |
Pro-apoptosis solid dispersion comprises a Bcl-2 family protein as defined herein, dispersed in a solid matrix comprising (a) a pharmaceutically acceptable water soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant, Inhibition Compounds of formula I are included in essentially amorphous form. The method of making such a solid dispersion comprises the steps of: providing an extrudable semi-solid mixture by applying an elevated temperature to the compound of formula (I), the water soluble polymeric carrier and the surfactant; Extruding the semi-solid mixture; And cooling the resulting extrudate to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in an essentially amorphous form. The solid dispersion is suitable for oral administration to a subject in need thereof for the treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example, cancer or an immune disorder or autoimmune disease Do. |