Transdermal delivery of pergolide from surfactant-based elastic and rigid vesicles: characterization and in vitro transport studies.
OBJECTIVE
The aim of this study was to investigate the effect of elastic and rigid vesicles on the penetration of pergolide across human skin.


METHODS
Vesicles used consisted of the bilayer-forming surfactant L-595 (sucrose laurate ester) and the micelle-forming surfactant PEG-8-L (octaoxyethylene laurate ester), together with the stabilizer sulfosuccinate. A series of L-595/PEG-8-L/sulfosuccinate vesicles were investigated, ranging from very rigid to very elastic. Pergolide-loaded elastic and rigid vesicles were visualized using Cryo-TEM and characterized for size and stability. Transdermal penetration of pergolide from different vesicle compositions was studied in vitro using flow-through Franz diffusion cells. A saturated buffer solution served as the control.


RESULTS
Vesicle composition had a major effect on the physicochemical characteristics, morphology and drug solubility of the vesicular system. L-595/PEG-8-L/sulfosuccinate (70/30/5) elastic vesicles gave the best balance between vesicle stability and elasticity, as well as the highest drug solubility. Transport studies clearly showed that elastic vesicles were superior to rigid vesicles. Elastic vesicles enhanced the drug transport compared to the buffer control, although rigid vesicles decreased the drug transport. The best drug transport was achieved from L-595/PEG-8-L/sulfosuccinate (70/30/5) elastic vesicles, resulting in a steady-state flux of 13.6 +/- 2.3 ng/ (h*cm2). This was a 6.2-fold increase compared to the most rigid vesicles.


CONCLUSIONS
This study supports the hypothesis that elastic vesicles are superior to rigid vesicles as vehicles for transdermal drug delivery.
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
P Loan
PL
Honeywell-Nguyen
Peter M
PM
Frederik
Paul H H
PH
Bomans
Hans E
HE
Junginger
Joke A
JA
Bouwstra
D000279:Administration, Cutaneous; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D004548:Elasticity; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D010479:Pergolide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D008823:Micelles; D013501:Surface-Active Agents; D010479:Pergolide