Leveque N, Raghavan S L, Lane M E, Hadgraft J
Laboratoire d'Ingenierie et de Biologie Cutanees, Faculté de Medecine et de Pharmacie, 25000 Besancon, France.
Int J Pharm. 2006 Aug 2;318(1-2):49-54. doi: 10.1016/j.ijpharm.2006.03.015. Epub 2006 Mar 22.
Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.
研究了利用“分子形式”技术形成的水杨酸（SA）过饱和溶液的渗透增强作用。在传统的助溶剂技术中，使用两种溶剂，其中一种溶剂中药物的溶解度远高于另一种。丙二醇和水主要用作助溶剂以在皮肤渗透增强中产生过饱和。在本文中，我们报道了使用不同pH值的缓冲溶液作为产生不同分子形式的介质。使用pH 8:pH 2（80:20 v/v）制备过饱和溶液，混合后标称pH约为5。使用了模型硅酮膜和人体皮肤。采用羟丙基甲基纤维素（HPMC）来稳定过饱和状态。稳定性数据表明，不含HPMC的SA过饱和溶液根据过饱和度在15分钟至46小时内结晶，而含HPMC的溶液稳定超过2个月。对于在80:20缓冲液pH 8/缓冲液pH 2混合物中制备的溶液，SA的通量随饱和度增加。尽管含和不含HPMC的SA通过硅酮膜和人体皮肤的通量相似，但发现HPMC可有效提高SA过饱和溶液的稳定性。
