Application of Design of Experiments to Optimizing Novel Gastroretentive Drug Delivery of Simvastatin

Abstract

Simvastatin is a hypolipidemic drug used in atherosclerosis. It has short elimination half life (2-3 hours) and narrow absorption window. It is mainly absorbed from stomach. The objective of this research was to develop gastroretentive floating tablets of Simvastatin using combination of release retardant polymers like Polyox WSR 205, Polyox WSR N12K and HPMC K4M. 3(2) full Factorial design was applied to design the experiments and tablets were prepared by direct compression. Prepared floating tablets were evaluated for hardness, floating time, friability, % drug content, swelling index, in-vitro drug release study and mean gastric retention period by invivo X-ray study. Statistical analysis was done using design expert software and model fitting was carried out using PCP DISSO. Design expert software was validated by comparing predicted results with observed results. Statistical analysis data revealed that tablets from formulation batch D3 (containing HPMC K4M 10% and POLYOX WSR 205 35%) and formulation batch E2 (HPMC K4M 10% and Polyox WSR N12K 25%) were promising system exhibiting excellent floating properties and drug release pattern. Stability studies revealed that all formulations were physically and chemically stable. In-vivo X-ray imaging of formula D3 and formula E2 shows mean gastric retention time of 6 ± 0.5 hours.