| 主权项 |
1. A composition, comprising:
(a) a first solid amorphous dispersion comprising a low-solubility drug and a concentration-enhancing polymer, wherein said low-solubility drug is dispersed in said concentration-enhancing polymer, wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, carboxymethyl ethyl cellulose, hydroxypropyl methyl cellulose, poloxamers, polyvinylpyrrolidone, polyvinyl alcohols that have at least a portion of their repeat units in hydrolyzed-form, and mixtures thereof; and (b) a second solid adsorbate blended with the first solid amorphous dispersion, the solid adsorbate comprising a water immiscible lipophilic microphase-forming material adsorbed onto a porous substrate, the water immiscible lipophilic microphase forming material comprising a mixture of a hydrophobic material selected from medium-chain glycerol mono-, di-, and tri-alkylates, sorbitan esters, sorbitan fatty acid esters, or a mixture thereof, and an amphiphilic material selected from polyoxyethylene sorbitan fatty acid esters, alpha tocopheryl polyethylene glycol 1000 succinate, or mixtures thereof, said lipophilic microphase-forming material being capable of forming a separate phase within an in vitro or in vivo aqueous use environment; and wherein said composition has a mass ratio of said lipophilic microphase-forming material to said low solubility drug of from 0.1 to 100; and wherein said lipophilic microphase-forming material is present in a sufficient amount so that said composition provides concentration enhancement of said drug in said aqueous use environment of at least 1.25-fold relative to both a first control composition and a second control composition, wherein (i) said first control composition consists essentially of an equivalent amount of said solid amorphous dispersion with no lipophilic microphase-forming a material present; and (ii) said second control composition consists essentially of an equivalent amount of said low-solubility drug in undispersed form with an equivalent amount of said lipophilic, microphase-forming material but with no concentration-enhancing polymer. |
