Levodopa의 이온토포레시스 경피전달: 올레인산 마이크로에멀젼 및 에탄올의 투과증진 (Iontophoretic Delivery of Levodopa: Permeation Enhancement by Oleic Acid Microemulsion and Ethanol)

서지정보

· 발행기관 : 한국약제학회
· 수록지 정보 : Journal of Pharmaceutical Investigation / 38권 / 6호 / 373 ~ 380페이지
· 저자명 : 정신애, 곽혜선, 전인구, 오승열

초록

In order to develop optimal formulation and iontophoresis condition for the transdermal delivery of
levodopa, we have evaluated the effect of two permeation enhancers, ethanol and oleic acid in microemulsion, on transdermal
delivery of levodopa. In vitro flux studies were performed at 33oC, using side-by-side diffusion cell and full thickness
hairless mouse skin. Current density applied was 0.4 mA/cm2 and current was off after 6 hours application. Levodopa was
analysed by HPLC at 280 nm. The o/w microemulsions of oleic acid in buffer solution (pH 2.5 & 4.5) were prepared using
oleic acid, Tween 80 and ethanol. The existence of microemulsion regions were investigated in pseudo-ternary phase diagrams.
Contrary to our expectation, cumulative amount of levodopa transported from microemulsion (pH 2.5) for 10 hours
was similar to that from aqueous solution in all delivery methods (passive, anodal and cathodal). When pH of the microemulsion
was pH 4.5, cumulative amount of levodopa transported for 10 hours increased about 40% (anodal) to 50%
(cathodal), when compared to that from aqueous solution. Flux from pH 4.5 microemulsion showed higher value than that
from pH 2.5 in all delivery methods. These results seem to indicate that electroosmosis plays more dominant role than electrorepulsion
in the flux of levodopa at pH 2.5. The effect of ethanol on iontophoretic flux was studied using pH 2.5 phosphate
buffer solution containing 3% or 5% (v/v) ethanol. Flux enhancement was observed in passive and anodal delivery
as the concentration of the ethanol increased. Without ethanol, cathodal delivery showed higher flux than anodal delivery.
Anodal delivery increased the cumulative amount of levodopa transported 1.6 fold by 5% ethanol after 10 hours. However,
in cathodal delivery, no flux enhancement of levodopa was observed during current application and only marginal increase
in cumulative amount transported after 10 hours was observed by 5% ethanol. These results seem to be related to the
decrease in dielectric constant of the medium and the lipid extraction of the ethanol, which decrease the electroosmotic flow,
and thus decrease the flux. Overall, the results provide important insights into the role of electroosmosis and electrorepulsion
in the transport of levodopa through skin, and provide some useful informations for optimal formulation for levodopa.

영어초록

In order to develop optimal formulation and iontophoresis condition for the transdermal delivery of
levodopa, we have evaluated the effect of two permeation enhancers, ethanol and oleic acid in microemulsion, on transdermal
delivery of levodopa. In vitro flux studies were performed at 33oC, using side-by-side diffusion cell and full thickness
hairless mouse skin. Current density applied was 0.4 mA/cm2 and current was off after 6 hours application. Levodopa was
analysed by HPLC at 280 nm. The o/w microemulsions of oleic acid in buffer solution (pH 2.5 & 4.5) were prepared using
oleic acid, Tween 80 and ethanol. The existence of microemulsion regions were investigated in pseudo-ternary phase diagrams.
Contrary to our expectation, cumulative amount of levodopa transported from microemulsion (pH 2.5) for 10 hours
was similar to that from aqueous solution in all delivery methods (passive, anodal and cathodal). When pH of the microemulsion
was pH 4.5, cumulative amount of levodopa transported for 10 hours increased about 40% (anodal) to 50%
(cathodal), when compared to that from aqueous solution. Flux from pH 4.5 microemulsion showed higher value than that
from pH 2.5 in all delivery methods. These results seem to indicate that electroosmosis plays more dominant role than electrorepulsion
in the flux of levodopa at pH 2.5. The effect of ethanol on iontophoretic flux was studied using pH 2.5 phosphate
buffer solution containing 3% or 5% (v/v) ethanol. Flux enhancement was observed in passive and anodal delivery
as the concentration of the ethanol increased. Without ethanol, cathodal delivery showed higher flux than anodal delivery.
Anodal delivery increased the cumulative amount of levodopa transported 1.6 fold by 5% ethanol after 10 hours. However,
in cathodal delivery, no flux enhancement of levodopa was observed during current application and only marginal increase
in cumulative amount transported after 10 hours was observed by 5% ethanol. These results seem to be related to the
decrease in dielectric constant of the medium and the lipid extraction of the ethanol, which decrease the electroosmotic flow,
and thus decrease the flux. Overall, the results provide important insights into the role of electroosmosis and electrorepulsion
in the transport of levodopa through skin, and provide some useful informations for optimal formulation for levodopa.

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