Kemken J, Ziegler A, Müller B W
Department of Pharmaceutics and Biopharmacy, Christian-Albrecht-University, Kiel, FRG.
Methods Find Exp Clin Pharmacol. 1991 Jun;13(5):361-5.
Transdermal administration of drugs possesses several advantages in therapy, but is limited by generally poor penetration through the skin. The aim of this study was to assess whether in vivo transdermal absorption could be enhanced by using microemulsions (ME) as vehicles. Water uptake from the occluded skin changes the water-free microemulsion base (MEB) into a ME. The increasing content of water decreases the solubility of apolar drugs. This leads to in situ formation of a super-saturated ME that possesses a particularly high absorption rate due to the enhanced diffusion pressure of the drug. A saturated solution of the model drugs bupranolol (B) and timolol (T) in a water-free microemulsion base was applied to an clipped area of the dorsal skin of rabbits with an occlusive patch. Evaluations were made in comparison to matrix patches (M) containing 1.2 mg/cm2 B or 2.0 mg/cm2 T. The beta-blocker dose applied was 2.0 mg/kg body weight throughout the study. The measured parameter of the pharmacodynamic effect was the maximal heart rate (HR) after an i.v. bolus injection of a standard dose of isoproterenol. Observations were made in different intervals over a 10-h time period after application of the patches. The response to isoproterenol was calculated as beta-blocker effect. Faster increasing effects and higher maxima for both drugs was found after application in MEB compared to M. After administration of B and T in MEB the effects were found to be identical, with a maximum (85-90%) after 2 h. Application in M showed B to be less effective (34%, 10h no plateau) than T (74%, 10h). Therefore microemulsions represent an improved vehicle for transdermal administration of test drugs.
药物的经皮给药在治疗方面具有多个优点，但通常因药物透过皮肤的渗透性较差而受到限制。本研究的目的是评估使用微乳剂（ME）作为载体是否能够增强体内经皮吸收。来自封闭皮肤的水分吸收将无水微乳剂基质（MEB）转变为微乳剂。水分含量的增加会降低非极性药物的溶解度。这导致形成超饱和微乳剂，由于药物扩散压力增强，其具有特别高的吸收率。将模型药物布普萘洛尔（B）和噻吗洛尔（T）在无水微乳剂基质中的饱和溶液用封闭贴片施用于兔背部皮肤的剪毛区域。与含有1.2mg/cm² B或2.0mg/cm² T的基质贴片（M）进行比较评估。在整个研究中，β受体阻滞剂的给药剂量为2.0mg/kg体重。药效学效应的测量参数是静脉推注标准剂量异丙肾上腺素后的最大心率（HR）。在贴片应用后的10小时时间段内，以不同间隔进行观察。将对异丙肾上腺素的反应计算为β受体阻滞剂效应。与M相比，在MEB中应用后，两种药物的效应增加更快且最大值更高。在MEB中给予B和T后，发现效应相同，2小时后达到最大值（85 - 90%）。在M中应用时，B的效果（34%，10小时无平台期）低于T（74%，10小时）。因此，微乳剂是测试药物经皮给药的一种改进载体。
