Simultaneous production and co-mixing of microparticles of nevirapine with excipients by supercritical antisolvent method for dissolution enhancement

Microparticles of a poorly water-soluble model drug, nevirapine (NEV) were prepared by supercritical antisolvent (SAS) method and simultaneously deposited on the surface of excipients such as lactose and microcrystalline cellulose in a single step to reduce drug-drug particle aggregation. In the proposed method, termed supercritical antisolvent-drug excipient mixing (SAS-DEM), drug particles were precipitated in supercritical CO2 vessel containing excipient particles in suspended state. Drug/excipient mixtures were characterized for Surface Morphology, Crystallinity, drug-excipient physico-chemical interactions, and molecular state of drug. In addition. the drug content uniformity and dissolution rate were determined. A highly ordered NEV-excipient mixture was produced. The SAS-DEM treatment was effective in overcoming drug-drug particle aggregation and did not affect the crystallinity or physicochemical properties of NEV. The produced drug/excipient mixture has a significantly faster dissolution rate as compared to SAS drug microparticles alone or when physically mixed with the excipients. (C) 2009 Elsevier B.V. All rights reserved.