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

• Published in: Drug development and industrial pharmacy Vol. 43; no. 5; pp. 812 - 829
• Main Authors: Surampalli, Gurunath, Satla, Madhuchander, Nanjwade, Basavaraj K., Patil, Paragouda A.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04-05-2017
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biological Availability; Caco-2 Cells; Cell Line, Tumor; Flavonoids - pharmacology; Freeze Drying - methods; freeze-dried solid dispersion; Humans; Ileum - metabolism; Intestinal Absorption - drug effects; Intestinal Mucosa - metabolism; Jejunum - metabolism; morin; Olmesartan medoxomil; Olmesartan Medoxomil - pharmacokinetics; Olmesartan Medoxomil - pharmacology; P-glycoprotein; Permeability; P-glycoprotein; freeze-dried solid dispersion; morin; Olmesartan medoxomil; permeability
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2016.1220569

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 × 10
−6 
cm/s in jejunum than ileum (p < .01) at 100 µM with absorption enhancement of 1.31-fold together with enhanced (p < .01) secretory transport of 6.27 ± 0.27 × 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.
Conclusions: Our study demonstrated that increased solubilization through freeze-dried OLM-loaded solid dispersion together with efflux inhibition improved intestinal permeability to one system that might lead to novel solubilization and efflux pump inhibition as a novel alternative potential to increase oral absorption and bioavailability of OLM.