In Vitro and In Vivo Evaluation of Polymeric Micelles of Telmisartan - An Attempt to Improve Oral Bioavailability

Introduction: Telmisartan exhibits poor aqueous solubility, susceptibility to Pglycoprotein (P-gp) efflux, and low oral bioavailability. This study aimed to enhance its solubility, intestinal permeability, and systemic exposure by developing polymeric micelles using optimized polymer–surfactant combinations. Methods: Polymeric micelles were formulated using carbomer 934, Poloxamer 188, and Poloxamer 407 with a surfactant–cosurfactant blend (Labrafil and Labrasol). The thin-film hydration technique was employed for drug loading. The formulations were evaluated for particle size, zeta potential, drug loading efficiency, stability under physiological conditions, in vitro drug release, ex vivo intestinal diffusion, and pharmacokinetic performance in animal models. Results: The developed micelles exhibited a nanoscale size (<150 nm) and high drug-loading efficiency. Among the tested formulations, Poloxamer 188-based micelles showed superior performance with sustained drug release. Ex vivo studies demonstrated a 3.6-fold increase in intestinal diffusion compared to the pure drug. Pharmacokinetic evaluation revealed a 3.2-fold increase in C_max within 1 hour, indicating rapid and enhanced absorption. Discussion: The improved performance of Poloxamer 188 micelles can be attributed to enhanced solubilization, reduced P-gp-mediated efflux, and increased membrane permeability. The nanosized structure likely facilitated better interaction with the intestinal mucosa, contributing to improved drug transport and absorption. Conclusion: The developed polymeric micelles demonstrated stability under gastrointestinal conditions and significantly improved intestinal permeability and oral bioavailability of telmisartan. Poloxamer 188-based micelles represent a promising strategy for enhancing the therapeutic efficacy of poorly soluble drugs.