MANUFACTURING
Formulation and Evaluation of Solid Dispersion Containing Simvastatin Simvastatin is an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase. It catalyses the conversion of HMG-CoA to mevalonate, an early and ratelimiting step in the biosynthesis of cholesterol. Simvastatin belongs to BCS class II drug. To overcome this shortcoming, a solid dispersion is prepared using a carrier of PEG 6000 to potentially enhance the dissolution rate and extend drug absorption. The objective of the study is to increase the solubility by solid dispersion method and to compare dissolution of pure drug and solid dispersions. The present study is an attempt to enhance the solubility of Simvastatin by fusion (Melt) method using polyethylene glycol 6000 as carrier. The complex of Simvastatin with polyethylene glycol 6000 shows enhanced solubility than the pure drug in the ratio between drug: carrier is 1:2. The dissolution rate studies were performed in phosphate buffer pH 7 and the dissolution rate was found to be 99.94 ± 2.17 per cent for optimised formulation F5 at the end of 50 mins. It is concluded that dissolution of the Simvastatin could be improved by the solid dispersion and PEG 6000 based solid dispersions were more effective in enhancing the dissolution. Subrat Kumar Tripathy, Assistant Manager, Quality Assurance Department, Cadila Healthcare Limited Chinmaya Keshari Sahoo, Associate Professor, Department of Pharmaceutics, College of Pharmaceutical Sciences
S
olubility is an important physicochemical factor affecting absorption of drug and its therapeutic effectiveness. The poor aqueous solubility
of drugs is still now a challenge in formulation and development. Due to the poor aqueous solubility, the dissolution as well as bioavailability decrease which may be
insufficient. Bioavailability of poor water solubility drugs that undergo dissolution rate limited gastrointestinal absorption can generally be improved by formulation techniques, such as preparation of solid dispersions. Solid dispersion, in which compounds are dispersed into water-soluble carriers, has been generally used to improve the dissolution properties and the bioavailability of drugs that are poorly soluble in water. In the biopharmaceutical classification system (BCS) drugs with low aqueous solubility and high membrane permeability are categorised as Class II drugs. Therefore, solid dispersion technologies are particularly promising for improving the oral absorption and bioavailability of BCS Class II drugs. Drugs disperse in the matrix generally a hydrophilic matrix and a hydrophobic drug to form a solid dispersion. The carrier of solid dispersion dissolves in water very quickly. The drug release is high due to more surface area of particles which causes high bioavailability of poor water-soluble drugs. Polyethylene glycols (PEGs) with molecular weights of 1,500–20,000 are extensively used as water-soluble carriers for preparation of solid dispersions of many poorly water-soluble drugs. The carriers show low melting point, rapid solidification rate, low toxicity, low costs, and good solubility in water and most of organic solvents. The aim of a present study was to compare
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