Box Behnken Design-Enabled Development of Nanostructured Lipid Carrier Transdermal Patch for Enhancement of Bioavailability of Olmesartan Medoxomil

Objective

Olmesartan medoxomil is an antihypertensive agent used for the management of hypertension but it undergoes first-pass metabolism when taken orally and bioavailability is less than 28%. This can be overcome by choosing it for topical administration by loaded with nanostructured lipid carrier (NLC) and prolonging its action.

Methods

Nanostructured lipid carrier loaded with olmesartan was prepared by high-speed hot homogenization and melt emulsification low-temperature solidification method. The formulation was composed of solid lipid, liquid lipid, surfactants, and polymers. Formulation fabrication and optimization by Box Behnken design with Design Expert software version 8.0.0. The prepared NLC formulations were studied for drug loading, entrapment efficiency, transmission electron microscopy, zeta potential, and particle size and stability study. The transdermal patch loaded with NLC containing olmesartan was fabricated and optimized.

Results

The optimized NLC formulation of olmesartan was used to fabricate it into transdermal patches. The optimized formulation (NLC F13) was found to possess particle size, zeta potential, polydispersity index, and entrapment efficiency of 284 nm, − 24.16 mV, 0.8, and 80.17%, respectively. The prepared optimized NLC-loaded transdermal patch was evaluated for weight variation, folding endurance, drug content, and drug release; the results were found as 0.074 ± 0.003, 122 ± 2.56, 92.44 ± 1.89, and 94.24 ± 0.832, respectively. In vivo pharmacokinetic study was approved by IAEC Regd. No. 926/PO/Re/S/06/CPCSEA. The study was a comparison of the pure drug (oral), drug-loaded NLC (oral), and drug-loaded NLC patch (transdermal). It was found that AUC _0–24 and AUC _0-∞ of drug-loaded NLC patch were 17.257 ng. h/mL and 34.259 ng. h/mL as compared with pure drug for oral 8.603 ng. h/mL and 16.547 ng.h/mL, respectively. The AUC _0–24 and AUC _0-∞ of drug-loaded NLC for the oral route were found at 17.857 ng. h/mL and 29.727 ng. h/mL, respectively.

Conclusion

It was found that formulation was optimized successfully and the bioavailability of the drug enhances significantly as compared to the pure drug and drug-loaded NLC for the oral route. So, optimized formulation was a promising drug delivery system for the effective treatment of hypertension.