Improvement Of Dissolution And Bioavailability Characteristics Of Simvastatin Using Various Pharmaceutical Techniques

Abstract

The objective of present study was to improve the dissolution and bioavailability of Simvastatin newline(SIM), a BCS Class-II drug, by employing two pharmaceutical techniques viz., Solid Dispersion newline(SD) and Self emulsifying drug delivery system (SEDDS). newlineSIM is a suitable candidate for solubility enhancement because it exhibits low solubility (1.45 newlineand#956;g/mL) and low oral bioavailability (5%). SIM is crystalline in nature and is a lactone Prodrug. It newlinehas been stated that lactones have poor solubility in water in comparison with other statins. newlineHence, it is poorly absorbed from the gastrointestinal tract (GIT). SIM often displays dissolution newlinerate governing oral absorption and variations in pharmacological outcomes. Therefore, newlineimprovement in its solubility and dissolution rate may be a guiding step in bioavailability newlineenhancement. newlineSIM was characterized for organoleptic properties, melting point, partition coefficient and newlinespectral characterization viz., FTIR, DSC, UV for identification. The results establish the purity, newlineidentification and authenticity of the drug. newlineDissolution method for SIM was successfully validated as the dissolution medium reported in the newlineliterature (USP 32) was not discriminative. The method was optimized for concentration of SDS newlineand rotations per minute. The method was validated for specificity, linearity, accuracy as newlinerecovery, precision and robustness. The amount of SIM was estimated by HPLC and UV newlinemethods and the results were statistically compared in order to establish a befitting method for newlineanalyzing SIM. newline0.1 % SDS in dissolution medium was optimized as this concentration was able to display the newlineactual effect of formulation on the dissolution rate of drug. All results of the validation newlineparameters of developed dissolution medium were found to be satisfactory and in the acceptable newlinerange for both analytical methods. Linearity was found to be 4 -60 and#956;g/mL and 2 -16 µg/ml for newlineHPLC and UV methods respectively. The low value of RSD (lt2%) in both cases indicate that newlineboth the methods are adequate. Statistically, n