Department of Pharmacy, National University of Singapore, Singapore.
J Pharm Pharmacol. 2010 Jun;62(6):770-8. doi: 10.1211/jpp.62.06.0014.
The aim of this work was to study the effect of surface tension and contact angle on the permeation of haloperidol across human skin using cyclodextrin derivatives.
Surface tension and contact angle of randomly methylated beta-cyclodextrin (RM beta-CD) and hydroxypropyl beta-cyclodextrin (HP beta-CD) solutions were measured. Haloperidol solubility and molecular modelling were carried out using the two cyclodextrin derivatives. In-vitro skin permeation was carried out using human skin models.
The highest increase in drug solubility was observed when the drug was in solution with pH 5 when compared to non-ionised solution, resulting in a 128-fold increase in the intrinsic solubility of the drug. Surface tension measurements indicate a surface-active effect for RM beta-CD and HP beta-CD. Contact angle measurements showed that vehicles with higher skin wettability increased the contact of the drug with the skin surface and therefore resulted in higher drug permeation across human epidermis.
It is concluded that transdermal flux of a drug through the skin may be optimised by controlling surface tension, drug solubility and skin wettability.
本研究旨在使用环糊精衍生物研究表面张力和接触角对氟哌啶醇经人皮肤渗透的影响。
测量随机甲基-β-环糊精（RM-β-CD）和羟丙基-β-环糊精（HP-β-CD）溶液的表面张力和接触角。使用两种环糊精衍生物进行氟哌啶醇溶解度和分子建模。进行体外皮肤渗透实验。
与非离解溶液相比，当药物在 pH5 的溶液中时，药物的溶解度增加最大，导致药物的固有溶解度增加了 128 倍。表面张力测量表明 RM-β-CD 和 HP-β-CD 具有表面活性作用。接触角测量表明，具有更高皮肤润湿性的载体增加了药物与皮肤表面的接触，从而导致氟哌啶醇经人表皮渗透增加。
可以通过控制表面张力、药物溶解度和皮肤润湿性来优化药物经皮透过皮肤的通量。
