Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery.
A novel microemulsion was prepared to increase the solubility and the in vitro transdermal delivery of poorly water-soluble vinpocetine. The correlation between the transdermal permeation rate and structural characteristics of vinpocetine microemulsion was investigated by pulsed field gradient nuclear magnetic resonance (PFG-NMR). For the microemulsions, oleic acid was chosen as oil phase, PEG-8 glyceryl caprylate/caprate (Labrasol) as surfactant (S), purified diethylene glycol monoethyl ether (Transcutol P) as cosurfactant (CoS), and the double-distilled water as water phase. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of each component for the microemulsion formation. The effects of various oils and different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. Self-diffusion coefficients were determined by PFG-NMR in order to investigate the influence of microemulsion composition with the equal drug concentration on their transdermal delivery. Finally, the microemulsion containing 1% vinpocetine was optimized with 4% oleic acid, 20.5% Labrasol, 20.5% Transcutol P, and 55% double-distilled water (w/w), in which drug solubility was about 3160-fold higher compared to that in water and the apparent permeation rate across the excised rat skin was 36.4 +/- 2.1 microg/cm2/h. The physicochemical properties of the optimized microemulsion were examined for the pH, viscosity, refractive index, conductivity, and particle size distribution. The microemulsion was stable after storing more than 12 months at 25 degrees C. The irritation study showed that the optimized microemulsion was a nonirritant transdermal delivery system.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China. lh7618@21cn.com
L
L
Hua
P
P
Weisan
L
L
Jiayu
Z
Z
Ying
D000279:Administration, Cutaneous; D000818:Animals; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005989:Glycerides; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019301:Oleic Acid / Q000737:chemistry; D009930:Organic Chemicals; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
D004655:Emulsions; D005026:Ethylene Glycols; D005079:Excipients; D005989:Glycerides; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D013501:Surface-Active Agents; D014748:Vinca Alkaloids; C440220:Labrasol; D019301:Oleic Acid; C013983:vinpocetine; C010111:carbitol