title: Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol.
abstract: The current studies entail a novel approach of formulating the solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of carvedilol solely using rational blends of lipidic and emulsifying excipients without using equipment-intensive techniques and/or inert porous carriers. Delineating the nanoemulsion regions, the amounts of Capmul MCM (i.e., lipid) and Nikkol HCO 50 (i.e., emulgent) were selected as the critical factors for systematically formulating the optimized S-SNEDDS employing face centered cube design. The optimized formulation (mean globule size: 40.8 nm) indicated marked improvement in drug release profile vis-à-vis pure drug and marketed formulation. Augmentation in the values of C(max) (134.2%) and AUC (85.2%) indicated significant enhancement in the rate and extent of bioavailability by the S-SNEDDS formulation compared to pure drug. In situ SPIP studies ascribed the significant enhancement in absorptivity parameters of SNEDDS formulations to transport through the lymphatic system and reduced P-gp efflux. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC's) substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The optimized formulation was found to be quite stable during six months of study period. The current investigations, therefore, report the successful development of systematically optimized S-SNEDDS with enhanced bioavailability potential of carvedilol.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India. bsbhoop@yahoo.com
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Singh
authors.forename: Shantanu
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Rishi
authors.initials: R
authors.lastname: Kapil
authors.forename: Babita
authors.initials: B
authors.lastname: Garg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D007408:Intestinal Absorption; D008055:Lipids; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D011412:Propanolamines; D000077261:Carvedilol