IMPROVEMENT OF SIMVASTATIN SOLUBILITY USING NATURAL POLYMERS BY SOLID DISPERSION TECHNIQUE

Abstract

The solubility of the poorly soluble drugs can be improved by various techniques such as micronization[1], solubilization[2], salt formation[1], complexation[1] with polymers, change in physical form, use of prodrugs[1] and drug derivatization[1], pH alteration, addition of surfactants[3,4] , and others. Serajuadin [5] used the solid-dispersion technique for dissolution enhancement of poorly water-soluble drugs. A solid dispersion can be defined as “the dispersion of one or more active ingredients in an inert carrier matrix in solid-state prepared by a physical mixture, melting (fusion), solvent, or melting–solvent method,” while Corrigan[6] suggested it is “a product formed by converting a fluid drug–carrier combination to the solid state.” Among the various approaches, the solid-dispersion technique has often proved to be the most successful in improving the dissolution and bioavailability of poorly soluble, active pharmaceutical ingredients because it is simple, economical, and advantageous. Simvastatin (SIM), a crystalline compound, is practically insoluble in water and hence poorly absorbed from the GI tract [7,8] . It is a potent and specific inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase [9, 10], which catalyzes the reduction of HMG CoA to mevalonate. Thus, simvastatin arrests a key step for cholesterol biosynthesis in the liver and is widely used in the treatment of hypercholesterolemia and dyslipidemia as an adjunct to diet. After oral administration, Simvastatin is metabolized to its β-dihydroxy acid form (simvastatin acid) by the cytochrome-3A system in the liver, where it inhibits the rate-limiting step in cholesterol biosynthesis. This leads to up-regulation of low-density lipoprotein (LDL) receptors and an increase in catabolism of LDL cholesterol. Being a BCS Class II drug, it often shows dissolution rate-limited oral absorption and high variability in pharmacological effects. Therefore, improvement in its solubility and dissolution rate may lead to enhancement in bioavailability [11]. In the present study, of solid dispersion physical mixture technique was used and solubility of drug was improved by using some natural polymers like Xanthum gum, Guar gum, Karaya gum, Chitosan and Oats powder.