Skin penetration and mechanisms of action in the delivery of the D2-agonist rotigotine from surfactant-based elastic vesicle formulations.
OBJECTIVE
This study was performed to investigate the effect of elastic and rigid vesicles on the penetration of the D2 dopamine agonist rotigotine across human skin and to further elucidate the mechanisms of action of the elastic vesicles.


METHODS
A series of rotigotine-loaded vesicles were prepared, ranging from very elastic to very rigid. The drug penetration from these vesicles across human skin was studied in vitro using flow-through diffusion cells. Micelle and buffer solutions were investigated as controls. For the most elastic vesicle composition, two additional variables were investigated. Coapplication of drug and vesicles was compared to pretreatment, and the effect of the drug entrapment efficiency was investigated.


RESULTS
The very elastic vesicle formulation L-595/PEG-8-L (50/50) gave steady-state fluxes of 214.4 +/- 27.8 ng/(h x cm2). This formulation was the most effective formulation and significantly better than the rigid vesicle formulations as well as the micelle and buffer controls. However, coapplication and a high drug entrapment efficiency were essential factors for an optimal drug delivery from elastic vesicle formulations.


CONCLUSIONS
Elastic vesicles are promising vehicles for transdermal drug delivery. It is essential that drug molecules are applied together with and entrapped within the vesicles themselves, suggesting that elastic vesicles act as drug carrier systems and not solely as penetration enhancers.
Honeywell-Nguyen
P Loan
PL
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, 2300 RA Leiden, The Netherlands.
Arenja
Sonia
S
Bouwstra
Joke A
JA
D001692:Biological Transport; D004337:Drug Carriers; D004355:Drug Stability; D004548:Elasticity; D004952:Esters; D006801:Humans; D066298:In Vitro Techniques; D007848:Laurates / Q000494:pharmacology; D008823:Micelles; D010539:Permeability; D011092:Polyethylene Glycols / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012879:Skin Physiological Phenomena; D013386:Succinates / Q000494:pharmacology; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000493:pharmacokinetics*; D013997:Time Factors
D004337:Drug Carriers; D004952:Esters; D007848:Laurates; D008823:Micelles; D017448:Receptors, Dopamine D2; D013386:Succinates; D013501:Surface-Active Agents; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C018152:sucrose monolaurate; D011092:Polyethylene Glycols; D013395:Sucrose; C047508:rotigotine