Effects of ethyl cellulose and polyvinyl alcohol mass ratio on the release and permeation profiles of a simvastatin-loaded transdermal system

Simvastatin (SMV), a widely prescribed drug for the treatment of hypercholesterolemia, has low oral bioavailability due to poor aqueous solubility and extensive first-pass metabolism. Transdermal delivery of this drug is a promising alternative to increase its bioavailability. As part of preliminary formulation studies for a matrix-type transdermal system for SMV, this study aimed to investigate the effects of different mass ratios of ethylcellulose (EC) and polyvinyl alcohol (PVA) on SMV release and permeation. In vitro drug release was performed via USP dissolution apparatus 5. In vitro permeation was performed using a diffusion cell with Strat-M® as membrane. The formulation with the balanced release and permeation characteristics was further evaluated for thickness, weight uniformity, folding endurance, moisture content, SMV content, and adhesion characteristics. The formulations showed similar sustained release profiles within 24 h, with maximum release (95.30 ± 2.96%) exhibited by F4 containing 7:3 EC:PVA ratio, which was significantly different from formulations F1-F3 containing lower amounts of EC. Kinetic modeling shows similar non- Fickian release of SMV from all the formulations. In the permeation studies, F5 containing 9:1 EC:PVA ratio showed the highest quantity of SMV permeated (16.38%) and flux (0.6964 µg/cm2/h), but this was not statistically different from the permeation characteristics of F4. Based on release and permeation performance, formulation F4 is promising for further development. It also exhibited satisfactory physicochemical characteristics overall, but the adhesion performance remains to be improved in optimization studies.