Prajakta Raut, Makarand Gambhire*, Dhruvi Panchal and Vaishali Gambhire Pages 120 - 129 ( 10 )
Background: Mirabegron (MBN), a β-3 adrenergic agent, is used in the treatment of overactive bladder. MBN has alow water solubility, high first-pass metabolism, and low bioavailability, consequently having poor absorption in the gastrointestinal tract.
Objective: The present study is intended to formulate Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to bypass hepatic first-pass metabolism and to improve its oral bioavailability.
Methods: MBN-SLNs were developed using glyceryl monostearate by pre-emulsion-ultrasonication method, which was then optimized applying Box-Behnken Design. The optimized batch of MBN-SLN was selected for surface-modification with PEG-400 (MBN-PEG-SLN) and characterized by photon correlation spectroscopy, DSC, and XRD. Bioavailability studies were conducted in Wistar rats after oral administration of plain MBN dispersion, MBN-SLN, and MBN-PEG-SLN.
Results: Stable MBN-SLNs and MBN-PEG-SLN of the optimized batch having a mean particle size of 162.7 nm and 149.9 nm; zeta potential of -39.1 mV and -30.9 mV; % entrapment of 89.90% and 90.12%, respectively, were developed. The results of the in vitro drug release studies demonstrated a significant slow release of MBN from MBN-SLN (69.38%) and MBN-PEG-SLN (61.33%) as compared to the dispersion of pure drug (92.10%). The relative bioavailability, as a result of the in vivo studies, of MBN from MBN-PEG-SLN increased by 2-fold, based on the Cmax values, in comparison with the plain MBN dispersion.
Conclusion: Thus, the study established that the oral bioavailability of MBN could be improved by the administration of MBN-PEG-SLN. The obtained results indicate SLNs as a potential drug delivery system for improving the bioavailability of poorly bioavailable drugs such as MBN by abating the first-pass metabolism.
Mirabegron, solid lipid nanoparticles, pre-emulsion-ultrasonication, PEGylation, oral delivery, box-behnken design, bioavailability.
Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune