The aim of the present investigation was to develop a suitable matrix type transdermal drug delivery system of simvastatin in order to overcome their side effects by oral application. The feasibility of development of transdermal system of simvastatin was investigated. Penetration enhancing potential of natural (olive oil, sunflower oil and jojoba oil) and synthetic permeation enhancers (span 20, oleic acid and dimethylsulfoxide) on in-vitro permeation of simvastatin across rat skin was studied. A total of 18 matrix patches were prepared by using blends of HPMC K4M (a hydrophilic polymer) and ethylcellulose (a hydrophobic polymer), dibutylthalate as plasticizer and natural and synthetic permeation enhancers in chloroform and methanol (1:1) as a solvent system. The formulations were characterized including uniformity of weight, drug content, moisture content, moisture uptake, flatness, folding endurance and thickness to study the stability of the formulations and in vitro dissolution of the experimental formulations were also performed to determine the drug distribution in the matrix. Drug–excipient interaction studies were carried out using Fourier transform infrared (FTIR) spectroscopic technique. In vitro dissolution studies showed that the drug distribution in the matrix was homogeneous and it was found that the maximum drug release in 24 hrs was 95.28±1.24% with formulation B3 (containing 10% olive oil). In vitro skin permeation study was also conducted in a modified Franz's diffusion cell, the film F3 (span 20; 10%) exhibited the greatest % cumulative drug permeated (91.93 ± 2.03%) in 24 h, which was significant (p<0.05; t-test) than formulation containing no permeation enhancer. Optimized formulations (B3 and F3) were found to be suitable for formulating in terms of physicochemical characteristics and there was no significant interaction noticed between the drug and polymers used.
