Evaluation of solid state properties of solid dispersions prepared by hot-melt extrusion and solvent co-precipitation.

The solid state properties of solid dispersions of Compound A in hypromellose acetate succinate (HPMC-AS) prepared by hot-melt extrusion (HME) and solvent co-precipitation (CP) processes were evaluated using powder X-ray diffractometry (PXRD), thermal analysis, optical microscopy, scanning electron microscopy (SEM), FT-IR and Raman spectroscopy, water vapor sorption analyzer, and surface area by BET. PXRD indicated that both processes converted the crystalline drug into amorphous solid dispersions with a glass transition temperature around 104-107 degrees C and both products have similar spectroscopic and hygroscopic properties. The two products have similar true densities; however, the CP product is more porous and has a larger specific surface area than the HME product, as indicated by the BET results and SEM micrographs. Dissolution study using USP apparatus 2 showed that the CP product had a faster dissolution profile, but slower intrinsic dissolution rate than the HME product. The two products have acceptable physical stability after storage in 40 degrees C/75% RH chamber for 3 months. However, the HME product is more stable than the CP product in aqueous suspension formulation.

[1]  G. Zografi,et al.  Water vapor absorption into amorphous hydrophobic drug/poly(vinylpyrrolidone) dispersions. , 2002, Journal of pharmaceutical sciences.

[2]  T. Rades,et al.  Factors affecting incorporation of drug into solid solution with HPMCP during solvent change co-precipitation. , 2002, International journal of pharmaceutics.

[3]  Xing Tang,et al.  Part I: Characterization of Solid Dispersions of Nimodipine Prepared by Hot-melt Extrusion , 2007, Drug development and industrial pharmacy.

[4]  A. Serajuddin,et al.  Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. , 1999, Journal of pharmaceutical sciences.

[5]  J. Crison,et al.  A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability , 1995, Pharmaceutical Research.

[6]  O. El-Gazayerly Characterization and Evaluation of Tenoxicam Coprecipitates , 2000, Drug development and industrial pharmacy.

[7]  George Zografi,et al.  Effects of water vapor absorption on the physical and chemical stability of amorphous sodium indomethacin , 2004, AAPS PharmSciTech.

[8]  Lei Li,et al.  Characterization of Poly(Ethylene Oxide) as a Drug Carrier in Hot-Melt Extrusion , 2006, Drug development and industrial pharmacy.

[9]  R. Chokshi,et al.  Characterization of physico-mechanical properties of indomethacin and polymers to assess their suitability for hot-melt extrusion processs as a means to manufacture solid dispersion/solution. , 2005, Journal of pharmaceutical sciences.

[10]  George Zografi,et al.  Physical Properties of Solid Molecular Dispersions of Indomethacin with Poly(vinylpyrrolidone) and Poly(vinylpyrrolidone-co-vinyl-acetate) in Relation to Indomethacin Crystallization , 1999, Pharmaceutical Research.

[11]  Wei Yang,et al.  Hot-melt extrusion for enhanced delivery of drug particles. , 2007, Journal of pharmaceutical sciences.

[12]  T. Rades,et al.  Physical stability and enthalpy relaxation of drug‐hydroxypropyl methylcellulose phthalate solvent change co‐precipitates , 2003, The Journal of pharmacy and pharmacology.