Pharmaceutical Compositions For Poorly Water-Soluble Compounds

摘要

This present invention is concerned with novel solid dispersion pharmaceutical compositions for preparation of composition which is comprised of a compound with poor water solubility (a weakly basic, neutral and/or non-ionizable, or a weakly acidic compound), water-soluble polymer(s), pH-sensitive polymer(s) (either enteric polymer or gastric-soluble polymer that is soluble at gastric fluid and insoluble at intestine pH range such as Eudragit E), and/or pharmaceutical acceptable surfactant(s) that would improve the solubility/dissolution of the compound in aqueous media of both low and neutral pHs and provide a relative pH-independent dissolution profile.

主权项

1. A solid dispersion, which comprises at least one poorly water-soluble basic compound (API) with at least one pharmaceutically acceptable water-soluble polymer, at least one enteric polymer, and optionally at least one pharmaceutically acceptable surfactant;
wherein, in the absence of said solid dispersion, the poorly water-soluble basic compound has at least one pKa (base) within the range of 0.0-10.0, and a pH-dependent solubility in aqueous environment of pH 1.0-8.0 with the lowest aqueous solubility of <1.0 mg/mL at pH 6.0-8.0; wherein, in said solid dispersion, said enteric polymer(s) is dispersed in a solid dispersion matrix with API, water-soluble polymer(s) and/or surfactant(s) at a solid state; wherein, said polymer(s) and/or surfactant(s) are present in amounts such that the concentration of said dissolved poorly water-soluble basic compound at both pH 1.0-2.0 and pH 6.0-8.0 at or after 90 minutes time point during non-sink dissolution test in aqueous environment is at least 2 fold of the solubility of said API alone in aqueous environment at pH 6.0-8.0 not containing said solid dispersion;wherein, in said solid dispersion, said polymer(s) and/or surfactant(s) are present in amounts such that at or after 90 minutes time point after non-sink dissolution test in aqueous environment, the ratio of the concentration of said dissolved poorly water-soluble basic compound at pH 1.0-2.0 to that at pH 6.0-8.0 is less than 2.0.