Polymer Combination Increased Both Physical Stability and Oral Absorption of Solid Dispersions Containing a Low Glass Transition Temperature Drug: Physicochemical Characterization and in Vivo Study

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The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (Tg) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the Tg in proportion to polymer concentration. Experimental Tg values corresponded closely with theoretical Tg values; indeed, the Tg values of solid dispersion with HPMC did not increase significantly compared to the Tg value for the drug alone. A solid dispersion formulation incorporating two different polymers—HPMC and either PVP-VA or PVP—maintained increased Tg, physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-Tg drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.