Stabilization of amorphous state of indomethacin by solid dispersion in polyvinylpolypyrrolidone.

Abstract

Solid dispersion of indomethacin (IMC) in polyvinylpolypyrrolidone (PVPP), in which IMC is in an amorphous state, was prepared from an acetone solution of IMC containing PVPP in suspension, and the stability of the amorphous state of IMC dispersed in PVPP was investigated at various temperature and humidity levels in comparison with that of simple amorphous IMC. The crystallization process of IMC was investigated by powder X-ray diffractometry and differential scanning calorimetry. Without moisture, IMC dispersed in PVPP remained in the amorphous state for 6, 2 and 1 months at 40, 50, and 60°C, respectively. Simple amorphous IMC was readily converted to form I at 20, 30, 40, and 50°C in the absence of moisture. On the other hand, at relative humidity levels of 100 and 89%, IMC dispersed in PVPP was converted to form II in 7 and 28 d, respectively, at 30°C. The amorphous state of IMC was thus stabilized against heat and moisture in the solid dispersion in PVPP. This result suggests that fast-dissolving pharmaceutical preparations of IMC providing high bioavailability could be obtained by using solid dispersions in PVPP.