In vitro and in vivo effects of morin on the intestinal absorption and pharmacokinetics of olmesartan medoxomil solid dispersions

摘要

Purpose: In-situ evaluation to corroborate morin effects on the intestinal absorption and pharmacokinetic behavior of freeze-dried OLM-loaded solid dispersions with Caco-2 and in-vivo studies Methods: Intestinal transport and absorption studies were examined by Caco-2 permeability, in-situ single pass perfusion and closed-loop models along with in-vivo pharmacokinetic studies to evaluate and confirm the effect of P-gp-mediated activity of morin. We evaluated the intestinal membrane damage in the presence of morin by measuring the release of protein and lactate dehydrogenase (LDH) followed by using qualitative and quantitative morphometric analysis to describe the surface characteristics of intestinal epithelium. Results: Morin showed the highest P_(eff) value 13.8 + 0.34 x 10~(-6)cm/s in jejunum than ileum (p<.01) at 100 muM with absorption enhancement of 1.31-fold together with enhanced (p<.01) secretory transport of 6.27 ±0.27 x 10~(-6)cm/s in Caco-2 monolayer cells. Our findings noticed 2.37 {in-situ); 2.39 {in-vivo) and 1.43 (in-situ); 1.36 (In-vivo) fold increase in AUC_(0-t) with elevated C_(max) and shortened T_(max) for freeze-dried solid dispersion in the presence of morin as compared to pure OLM and freeze-dried solid dispersions without morin, respectively.