New intranasal cross-linked mosapride xyloglucan pluronics micelles (MOS-XPMs) for reflux esophagitis disease: In-vitro optimization and improved therapeutic efficacy

Abstract

Mosapride belongs to class IV in Biopharmaceutics Classification System and is used in the treatment of reflux esophagitis. It exhibits poor bioavailability due to limited permeability, solubility and extensive first-pass metabolism. In this study, intranasal mosapride-loaded cross-linked xyloglucan Pluronic micelles (MOS-XPMs) was formulated and optimized to improve the low solubility & bioavailability of MOS. The solid dispersion technique using 23 full factorial design was applied. (MOS-XPMs) (F4) had the highest desirability value (0.952) and, therefore, it was selected as an optimal system. Xyloglucan cross-linked in the shell of Pluronic micelles offered improved stability and mucoadhesiveness to MOS-XPMs. 1H NMR spectra ensured the cross-linking of xyloglucan with Pluronic micelle shell and micelle stabilization. A Pharmacodynamic study revealed that MOS-XPMs showed 1.5-fold increase in duodenal and cecal motility compared to MOS suspension and 1.7-fold increase compared to the oral marketed product. The new MOS-XPMs were shown to be successful at improving the therapeutic efficacy of mosapride. Keywords: Mosapride citrate, Xyloglucan Pluronic micelles, Intranasal administration, Gastrointestinal motility