COMPARATIVE STUDY OF REVERSE WET GRANULATION WITH CONVENTIONAL WET GRANULATION IN SOLUBILITY ENHANCEMENT OF SIMVASTATIN

摘要

Objectives : Simvastatin is a cholesterol- lowering agent widely used in hypercholesterolemia. It belongs to BCS class II drugs having low solubility and high permeability. Simvastatin is practically insoluble in water and poorly absorbed from the gastrointestinal tract. Therefore, it is necessary to introduce an effective method to enhance the solubility and dissolution rate of the drug. The main purpose of this work was to compare the reverse wet granulation with conventional wet granulation in enhancing the solubility of Simvastatin. Methods: The Granules were prepared by both conventional wet granulation in which Simvastatin was added along with other dry excipients and reverse wet granulation in which Simvastatin was added in granulating solvent using water as granulating solvent and Povidone, Lactose, Sodium starch glycolate, Magnesium stearate and Aerosil as an Excipients. The granules were evaluated for flow properties, solubility study, X- ray diffraction and FTIR study. Results: The flow properties of reverse wet granulation were found to be improved as compared to conventional wet granulation. The tablets were formulated from either type of granules which were subjected to a Hardness, Disintegration, Weight variation, Content of active ingredient, Friability, Wetting time and Dissolution test. The Simvastatin tablets of reverse wet granulation resulted in about 1.4 fold increase in dissolution rate when compared to conventional wet granulation tablets. The significant difference between flow properties and dissolution profile in between reverse wet granulation and conventional wet granulation was validated by statistical evaluation. Conclusion: Reverse wet granulation can be successfully used over the conventional wet granulation for solubility enhancement of Simvastatin. The method is easy to adopt. Keywords: Reverse wet granulation, Conventional wet granulation, Flow properties, Dissolution, Solubility, Wetting time.