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

摘要

The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T _g) 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 T _gin proportion to polymer concentration. Experimental T _g values corresponded closely with theoretical T _gvalues; indeed, the T _g values of solid dispersion with HPMC did not increase significantly compared to the T _gvalue for the drug alone. A solid dispersion formulation incorporating two different polymers - HPMC and either PVP-VA or PVP - maintained increased T _g, 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-T _g drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.