Formulation optimization and characterization of transdermal film of simvastatin by response surface methodology.

Matrix type of simvastatin transdermal film (SSTF) was developed with poly(vinyl alcohol) (PVA) and eudragit RL100 (EG) using response surface methodology (RSM) to investigate combined effect of the selected process variables like SS concentration, PVA:EG ratio and the dibutyl phthalate (DBT) concentration at different levels on dependent variables such as tensile strength and flux, with an aim to optimize a suitable combination of drug, polymer and plasticizer ratio. The study reveals that the effect of DBT concentration was highest on tensile strength, while SS concentration exhibited pronounced effect on SS flux through the abdominal skin of rat. According to Derringer's desirability prediction tool, the composition of optimized film was found to be 2% of SS, 2:1 ratio of PVA:EG and 40% of DBT. Under these conditions, the SSTF exhibited a predicted value of tensile strength and flux of 11.871 MPa and 43.569 μg/cm(2)/h, respectively. The in vivo hypolipidemic study conducted for 14 days in hyperlipidemia induced Sprague-Dawley rats reveals that the optimized SSTF exhibited significant lowering of blood lipid level. The absence of skin irritation indicates that the prepared film was safe and well tolerated as transdermal formulation. Thus, the film may serve as an alternative therapy to oral dosage form of SS.