Formulation Development and Evaluation of Simvastatin Sustained Release Tablets

Purpose: The main objective of present research investigation is to formulate the sustained release tablet of Simvastatin using 3² factorial design. Simvastatin, an antihyperlipidemic agent, belongs BCS class-II agent. Methods: The SR tablets of Simvastatin were prepared employing different concentrations of HPMCK4M and SCMC in different combinations by wet granulation technique using 32 factorial design. The concentration of Polymers, HPMCK4M and SCMC required to achieve the desired drug release was selected as independent variables, X₁ and X₂ respectively whereas, time required for 10% of drug dissolution (t_10%), 50% (t_50%), 75% (t_75%) and 90% (t_90%) were selected as dependent variables. Results and Discussion: Totally nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the Invitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept, slope & regression coefficient were calculated. Polynomial equations were developed for t_10%, t_50%, t_75%, t_90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C₁, C₂). According to SUPAC guidelines the formulation (F₄) containing combination of 17.5% HPMCK4M and 30% SCMC, is the most similar formulation (similarity factor f₂= 89.652, dissimilarity factor f₁= 1.6424 & No significant difference, t= 0.00558) to marketed product (ZOCOR). Conclusion: The selected formulation (F₄) follows Zero order, Higuchi's kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.963).