Spherical agglomeration a novel approach for solubility and dissolution enhancement of simvastatin

Abstract

Objective: Simvastatin is water insoluble drug commonly used in the treatment of hypercholesterolemia and dyslipidemia. The objective of the present investigation was to develop simvastatin spherical agglomerates to improve its solubility and dissolution characteristics by spherical agglomeration method. Methods: In preparation of simvastatin spherical agglomerates crystallization media used were methanol, water, and chloroform as bridging liquid and PVP K-30 as a polymer. The process variables such as amount and type of (bridging liquid and polymer), stirring speed, and stirring time were optimized. The spherical agglomerates were characterized by suitable analytical techniques and further subjected for determination of % drug content, particle shape analysis, solubility, and dissolution rate. The spherical agglomerates of the optimized batch were directly compressed into tablet; the dissolution profile of prepared tablet was compared with dissolution profile of marketed tablet. Result: The spherical agglomerates obtained with methanol (7 ml), water (50 ml), chloroform (1.5 ml), and PVP K-30 (0.5%) at 500 rpm and 15 minutes stirring time showed significant improvement in solubility and dissolution from a value of 0.029 mg/ml and 25.53% for pure simvastatin to 6.42 mg/ml and 91.31% of spherical agglomerate, respectively. The simvastatin tablet obtained with spherical agglomerates showed 89.65% cumulative drug release as compare to 80.28% of marketed tablet. Conclusion: A significant result obtained with the study indicates that spherical crystallization by spherical agglomeration technique can successfully be further explored and employed to improve solubility and dissolution characteristic of poorly soluble drugs.