Nanoemulsion system for the transdermal delivery of a poorly soluble cardiovascular drug.
The purpose of the present study is to develop and evaluate the potential of nanoemulsions for increasing the solubility and the in vitro transdermal delivery of carvedilol. Pseudoternary phase diagrams were developed and various nanoemulsion formulations were prepared using oleic acid and isopropyl myristate (IPM) (1:1) as the oil, Tween 80 as surfactant, and Transcutol P as cosurfactant. The prepared nanoemulsions were subjected to physical stability tests. Transdermal permeation of carvedilol through rat abdominal skin was determined with Keshary-Chien diffusion cell. Significant increase (P < 0.05) in the steady state flux (Jss) and permeability coefficient (Kp) was observed in nanoemulsion formulations as compared to control or drug-loaded neat components. The highest value of these permeability parameters was obtained in optimized formulation B3, which consisted of 0.5% w/w of carvedilol, 6% w/w of oleic acid:IPM (1:1), 22.5% w/w of Tween 80, 22.5% w/w of Transcutol P, and 49% w/w of distilled water and in which the solubility of the drug was 4500-fold higher. The optimized nanoemulsion was characterized for pH, conductivity, viscosity, droplet size, droplet shape, and refractive index. Thermodynamic studies showed that there had been a significant decrease of 88% in activation energy (Eact) when the drug was incorporated in nanoemulsion. The irritation studies suggested that the optimized nanoemulsion was a non-irritant transdermal delivery system.
Dixit
Nitin
N
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
Kohli
Kanchan
K
Baboota
Sanjula
S
D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D008657:Metabolic Clearance Rate; D051379:Mice; D010539:Permeability; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012882:Skin Tests; D012995:Solubility
D000959:Antihypertensive Agents; D002227:Carbazoles; D004655:Emulsions; D011412:Propanolamines; D000077261:Carvedilol