title: In vitro and in vivo effects of morin on the intestinal absorption and pharmacokinetics of olmesartan medoxomil solid dispersions.
abstract: OBJECTIVE
  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 Peffvalue 13.8 ± 0.34 × 10-6cm/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 × 10-6cm/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 AUC0-twith elevated Cmaxand shortened Tmaxfor 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.
authors.affiliation: a Department of Pharmacology and Toxicology , Vaagdevi Institute of Pharma Sciences , Telangana, Warangal , India.
authors.forename: Gurunath
authors.initials: G
authors.lastname: Surampalli
authors.affiliation: b Department of Obstetrics and Gynecology , Kakatiya Medical College , Warangal, Telangana , India.
authors.forename: Madhuchander
authors.initials: M
authors.lastname: Satla
authors.affiliation: c Department of Pharmacy Practice , The Oxford College of Pharmacy , Bengaluru , Karnataka , India.
authors.forename: Basavaraj K
authors.initials: BK
authors.lastname: Nanjwade
authors.affiliation: d Department of Pharmacology , USM-KLE, International Medical Program , Belgaum , Karnataka , India.
authors.forename: Paragouda A
authors.initials: PA
authors.lastname: Patil
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D005612:Freeze Drying / Q000379:methods; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D000068557:Olmesartan Medoxomil / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010539:Permeability; D047309:Flavones
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D000068557:Olmesartan Medoxomil; C008548:morin; D047309:Flavones
keywords: Olmesartan medoxomil; P-glycoprotein; freeze-dried solid dispersion; morin; permeability