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
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.