title: Positively charged self-nanoemulsifying oily formulations of olmesartan medoxomil: Systematic development, in vitro, ex vivo and in vivo evaluation.
abstract: The current research work explores the potential applications of cationic self-nanoemulsifying oily formulations (CSNEOFs) for enhancing the oral bioavailability of olmesartan medoxomil. Initial preformulation studies, risk assessment and factor screening studies revealed selection of oleic acid, Tween 40 and Transcutol HP as the critical factors. Systematic optimization of SNEOFs was carried out employing D-optimal mixture design and evaluating them for responses viz. emulsification efficiency, globule size and in vitro drug release. The CSNEOFs were prepared from the optimized SNEOFs by adding oleylamine as cationic charge inducer. In vitro cell line studies revealed markedly better drug uptake along with safer and biocompatible nature of CSNEOFs than free drug suspension. In situ perfusion, and in vivo pharmacokinetic and pharmacodynamic studies in Wistar rats revealed significant improvement in the biopharmaceutical performance of the drug from CSNEOFs and SNEOFs vis-à-vis the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the present studies report successful development of CSNEOFs of olmesartan medoxomil with distinctly improved biopharmaceutical performance.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160 014, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160 014, India.
authors.forename: Gajanand
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab 160 062, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Thanki
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab 160 062, India.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160 014, India.
authors.forename: O P
authors.initials: OP
authors.lastname: Katare
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160 014, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160 014, India. Electronic address: bsbhoop@yahoo.com.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000033:anatomy & histology / Q000187:drug effects; D019301:Oleic Acid / Q000737:chemistry; D000068557:Olmesartan Medoxomil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011136:Polysorbates / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047228:Angiotensin II Type 1 Receptor Blockers; D004655:Emulsions; D005026:Ethylene Glycols; D011136:Polysorbates; D019301:Oleic Acid; D000068557:Olmesartan Medoxomil; C010111:carbitol; C068430:polysorbate 40
keywords: Bioavailability; Design of experiments; In vitro cytotoxicity; Nanomedicine; Quality by Design; Self-nanoemulsifying