Spherical crystallization of ezetimibe for improvement in physicochemical and micromeritic properties

摘要

Spherical agglomerates of ezetimibe (EZT) were prepared with hydrophilic polymers; polyvinyl pyrrolidone K30 (PVP) and/or poloxamer 188 (poloxamer) at drug to polymer ratios of 1:1 (w/w) by spherical crystallization technique, in order to improve its physicochemical and micromeritic properties. Three different bridging liquids; chloroform, dichloromethane and/or ethyl acetate along with good solvent acetone and poor solvent water were used to form six batches of agglomerates. Initial characterization of all batches in terms of micromeritic and physicochemical properties resulted in optimization of (A3, EZT:PVP:ethyl acetate) and (B3, EZT:poloxamer:ethyl acetate) batches and hence further investigated for drug-polymer interaction, crystallinity and morphology using FTIR, XRPD, DSC and SEM techniques. The results indicated presence of hydrogen bonding, crystallinity and spherical shape in agglomerates. Therefore, the optimized agglomerates (B3) were directly compressed into tablet. Unfortunately, drug release from the tablet was not satisfactory, suggesting a need of disintegrant from dissolution point of view. Therefore, these agglomerates were recompressed incorporating certain excipients and evaluated as per pharmacopoeia. The dissolution rate of prepared tablet was similar to that of marketed tablet (p > 0.05). It could be concluded that spherical crystallization could be one of the effective and alternative approaches for improved performance of EZT and its tablet formulation.