Pharmacokinetic Study of Matrix Membrane Moderated Transdermal System of Bosentan Monohydrate

Objective: The objective of the present research work is to carry out the pharmacokinetic studies of optimized matrix membrane moderated transdermal patches of bosentan monohydrate.

Background: Bosentan monohydrate is the new generation endothelin receptor antagonist used to treat pulmonary arterial hypertension (PAH). Transdermal drug delivery had peculiar advantages compared to the oral route where the drug-induced toxicity can be moderated simply by removing the patch; it can be given to unconscious and nauseating patients.

Methods: The matrix membrane moderated transdermal system was formulated using HPMC K4M and E RLPO. In vitro diffusion studies were carried out using a modified Franz diffusion cell and for the optimized transdermal patch pharmacokinetic studies were carried out using New- Zealand male rabbits. Plasma samples were quantified using high-performance liquid chromatography.

Results: The In vitro diffusion studies revealed that formulation F3 with HPMC and E RLPO had controlled release up to 28 h and a maximum of 95.02±2.68 % drug was released. The release kinetics followed mixed order non-fickian diffusion. The pharmacokinetic studies of the optimized patch revealed controlled release up to 45 h where a 2.2-fold increase in AUC and 3.8 times increase in MRT were observed compared to the oral route. The results have appeared to be significant at p<0.05. The variation in half-life was found to be not statistically significant when compared between oral and transdermal routes. Pharmacokinetic modeling will give quantitative information regarding the plasma kinetic profile of the drug which can be used simultaneously in the pharmacodynamics modeling of the newly designed dosage form.

Conclusion: The matrix membrane-regulated transdermal system with extended AUC and MRT can improve the bioavailability of bosentan monohydrate by reducing drug-related side effects when taken orally, according to the pharmacokinetic data.