Preparation of the Solid Dispersion of Indomethacin with Phosphatidylcholine by Heating Method.

Abstract

The solid dispersion (SD) preparation method of indomethacin (IM, mp 161°C) with phosphatidylcholine (PC) was investigated. The melting point of PC is high, above 200°C, making a melting method inapplicable. However, PC shows a phase transition at about 100°C when its acyl chains are stearic acid and it is an anhydride. In the case of mole fraction of IM in SD being 0.50, X-ray diffraction patterns suggest that IM is in an amorphous state after heating at 90°C for 1h, at 110°C for 10min or at 180°C for 6min. When the mole fraction of IM is as low as 0.25 or 0.33, IM is also present in an amorphous state after heating at 70°C for 2h and at 90°C for 10min. The obtained SD showed endothermic peaks from about 40°C to 70°C upon thermal analysis. It is possible to prepare SD above 70°C, but this requires a long heating time; therefore, heating at above the phase transition temperature is most suitable. The dissolution patterns of IM from SD compressed into tablet form were fitted to Higuchi's square root equation and the dissolution rate was found to be 1.5-fold that from a physical mixture of the same composition.