In Vitro and In Vivo Characterization of Transdermal Patch Loaded with Nanostructured Lipid Carrier for Bioavailability Enhancement of Dolutegravir Sodium Using Taguchi and Box-Behnken Design

The objective of the present research work was to enhance the bioavailability of dolutegravir sodium (anti-HIV drug) by loading the drug into a nanostructured lipid carrier (NLC), fabricated into the patch, and administered through a transdermal route. For this experimental work, six solid lipids, ten liquid lipids, and nine surfactants were selected for initial screening. The hot high-shear homogenization and melt emulsification low-temperature solidification methods were used to prepare nanostructured lipid carrier formulation. A Taguchi screening method was employed to find out the most influencing factors on critical quality attributes (CQAs) followed by a Box-Behnken design was applied to find the relationship between the independent variables and dependent variables. The selected optimized NLC formulation was characterized, and fabricated into the transdermal patch, and evaluated in a rabbit model for various pharmacokinetic parameters. The optimized formulation was characterized for particle size, zeta potential and polydispersity index (PDI), X-ray diffraction study, transmission electron microscopy analysis, in vitro drug release study, and in vivo pharmacokinetic parameter analysis. The results revealed that the particle size was 151.1 nm, zeta potential - 19.3 mV, and PDI was found to be 0.292. The AUC ((0-8)) value of the drug-loaded NLC patch was 8156.426 ng h/ml, whereas 3945.696 ng h/ml and 4751.556 ng h/ml for pure drug and drug-loaded NLC formulation. From the experimental results, it was concluded that the NLC-loaded patch showed better bioavailability, which is nearly twice that of the pure drug administered by oral route. Hence, a fabricated NLC patch will be an assured drug delivery system for ameliorating the bioavailability of dolutegravir.