Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release

Abstract

The objective was to use caffeine and Soluplus® to improve the dissolution rate and to maintain a concentration of BCS Class II rosuvastatin calcium that exceeds its solubility. Caffeine and Soluplus® together substantially improved the dissolution rate and the extent of rosuvastatin release. Formulations for direct compression tablets included Formulation F1, a control with drug but with neither caffeine nor Soluplus® present; F2 with drug-caffeine complex; F3 with drug and Soluplus® and F4 with drug-caffeine complex and Soluplus®. Each formulation blend provided satisfactory flow properties. Tablets were comparable in mass, hardness and friability. A marked decrease in disintegration time occurred when the hydrotropic or micellar agent was included in the formulation. Assay (98–100%) and content uniformity (99–100%) results met requirements. Release studies in pH 1.2, 6.6, and 6.8 buffers revealed the superiority of F4. At 45 min sampling time, F3 and F4 tablets each provided a cumulative drug release greater than 70% in each medium. F2 tablets exhibited compliance to official standards in pH 6.6 and 6.8 buffers but not in pH 1.2 buffer, whereas tablets based on F1 failed in each medium. Two-factor ANOVA of the release data revealed a statistical difference across the four formulations in each release medium. Pairwise comparison of release profiles demonstrated that, of the four formulations, F4 provided the most effectively enhanced dissolution rate, improvement to the extent of drug release and support of a concentration higher than the solubility of rosuvastatin calcium.