Physicochemical Properties of Indomethacin and Related Compounds Co-Spray Dried with Polyvinylpyrrolidone

Abstract

The spray drying of indomethacin produced a viscous liquid phase which then solidified to an amorphous glassy solid mass. This amorphous phase was physically unstable and converted on storage to crystalline indomethacin forms II and I. Co -spray drying indomethacin with up to 20% PVP also gave a fused amorphous solid. Apparent solubility and dissolution studies illustrated the higher energy of indomethacin in these systems. The presence of PVP in the solid retarded conversion of indomethacin to a crystalline phase, the effect increasing with increasing PVP content. Scanning electron microscopy revealed the growth, with time, of needle-like whiskers on the surface of the amorphous products. Co-spray drying indomethacin with more than 20% PVP resulted firstly in products composed of a fused network of spherical particles, then partially coalesced spheres and ultimately, above 25% PVP, in individual agglomerated microspherical particles. The spray drying of either naproxen, ketoprofen or ibuprofen did not result in the formation of an amorphous glassy solid, Co-spray drying with PVP led to reduced crystallinity; the size of the melting endotherm decreased with increasing PVP content and became absent at 50% PVP. As the PVP percentage increased a microspherical product also developed, but at PVP levels greater than that observed for indomethacin.