Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential.
Carvedilol, a widely prescribed cardiovascular drug for hypertension and congestive heart failure, exhibits low and variable bioavailability owing to poor absorption and extensive hepatic first-pass metabolism. The current research work, therefore, entails formulation development of liquid self-nano-emulsifying drug delivery systems (SNEDDS) to enhance the bioavailability of carvedilol by facilitating its transport via lymphatic circulation. The formulation constituents, i.e. lipids, surfactants, and co-surfactants, were selected on the basis of solubility studies. Pseudo-ternary phase diagrams were constructed to embark upon the selection of blend of lipidic (i.e. Capmul PG8) and hydrophilic components (i.e. Cremophor EL as surfactant and Transcutol HP as co-surfactant) for efficient and robust formulation of SNEDDS. The SNEDDS, systematically optimized employing a central composite design (CCD), were evaluated for various response variables viz drug release parameters, emulsification time, emulsion droplet size, and mean dissolution time. In vitro drug release studies depicted that the release from SNEDDS systems followed a non-Fickian kinetic behavior. The TEM imaging of the optimized formulation affirmed the uniform shape and nano size of the system. Accelerated studies of the optimized formulation indicated high stability of the formulation for 6 months. The in situ perfusion studies carried out in wistar rats construed several fold augmentation in the permeability and absorption potential of the optimized formulation vis-à-vis marketed formulation. Thus, the present studies ratified the potential of SNEDDS in augmenting the oral bioavailability of BCS class II drugs.
University Institute of Pharmaceutical Sciences-UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India. bsbhoop@yahoo.com
Bhupinder
B
Singh
Lalit
L
Khurana
Shantanu
S
Bandyopadhyay
Rishi
R
Kapil
O O P
OO
Katare
D000818:Animals; D001682:Biological Availability; D002210:Caprylates / Q000737:chemistry; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D010477:Perfusion; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D002210:Caprylates; D002227:Carbazoles; D002317:Cardiovascular Agents; D004655:Emulsions; D005026:Ethylene Glycols; D005079:Excipients; D005989:Glycerides; D009821:Oils; D011412:Propanolamines; D000077261:Carvedilol; C000515:cremophor EL; C010111:carbitol; D005990:Glycerol; C025343:monooctanoin