Solid Dispersions of Indomethacin and Griseofulvin in Non-porous Fumed Silicon Dioxide, Prepared by Melting.

Abstract

A method of increasing the dissolution rates of glass-forming, poorly water-soluble drugs was investigated. It is based on the concept of preparing the powder form of a glassy drug dispersed in an inert carrier by melting. Indomethacin (IMC) and griseofulvin were used as model drugs, and fumed silicon dioxide was used as the carrier. The drug-silica (1 : 2) mixture was heated until the drug melted. The properties of the solid dispersion thus obtained were examined using powder X-ray diffractometry (XRD), differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and scanning electron microscopy (SEM). XRD showed that the drugs were converted from a crystalline state to an amorphous state in the solid dispersions. On DSC thermograms, a pure IMC glass showed an endothermic peak corresponding to glass transition, then an exothermic peak corresponding to transformation to a metastable crystal and an endothermic peak corresponding to melting of the metastable form. The IMC-silica solid dispersion, however, shows no transition peak in its thermogram, indicating that a solid dispersion is more stable to heat than pure glass. The drug-silica solid dispersions showed IR spectra characteristic of pure amorphous drugs but somewhat different from those of crystalline drugs. SEM revealed that the drug-silica solid dispersions had none of the characteristics observed in crystalline drugs. The dissolution rates of drugs from the solid dispersions were much higher than those from physical mixtures and from pure crystalline drugs.