New binary solid dispersion of indomethacin with surfactant polymer: From physical characterization to in vitro dissolution enhancement

This article investigated preparation of solid dispersions containing a poor water-soluble drug, indomethacin (IND), and a new surfactant polymer, polyoxyethylene 32 distearate (POED). Solid dispersions were prepared by the melting method and characterized by DSC, hot-stage microscopy (HSM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). DSC and HSM analyses performed on IND/POED physical mixtures indicated that IND could dissolve in liquid POED. The materials showed complete miscibility at liquid state. Combination of DSC, XRD, and SEM revealed that these materials had limited miscibility at the solid state. Up to 20% w/w IND in POED, we did not detect significant modification of physical properties of the polymer. It supports the formation of a solid solution of IND in solid POED. Above 20% w/w, the solid dispersions presented particular behavior upon heating (recrystallization of IND) and at the solid state (presence of some IND crystallites). Under 3-month storage at 25°C/53% RH, the solid dispersions demonstrated a good stability of the samples. Finally, in vitro dissolution studies showed that IND release was greatly improved (5.5–12 times as fast) by formation of solid dispersion. This enhancement was principally attributed to the high dispersion of IND in POED and to the polymer surfactant properties. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1399–1413, 2010