Nanocrystalline Solid Dispersions of Indomethacin with Hydrophilic Polymers

Abstract

Nanocrystalline solid dispersions (NCSDs) of Indomethacin were prepared by antisolvent precipitation followed by spray drying, using hydrophilic polymers like polyvinyl pyrrolidine (PVP K30), hydroxyl propyl methyl cellulose (HPMC E15) and polyvinyl alocohol (PVA) in the ratio of 90:10 w/w. Methonolic solution of Indomethacin was added to aqueous polymeric solution to obtain nano-crystals of Indomethacin, and was spray dried to obtain NCSDs. Crystallite size of Indomethacin in dispersion was measured using by Scherrer equation, which uses powder X-ray diffraction peak broadening of nano-crystallites over micro-crystallites. The average crystallite size of Indomethacin in dispersions was lowest in PVA dispersion followed by HPMC E15 and PVP K30. NCSDs showed considerably higher dissolution rate over crystalline solid dispersions and "as received" Indomethacin in water. NCSDs released 80 - 90% of Indomethacin within 10 min in comparison to 25-50% in case of crystalline solid dispersion and < 5% incase of "as received" Indomethacin. Higher dissolution efficiency of nanocrystalline solid dispersions could be attributed to the nano-size of Indomethacin crystallites, and crystal growth inhibition role of polymers. Influence of viscosity and drug-excipient miscibility (solubility parameter), of polymers used in the present study, on the crystallite size is discussed.