ESTRADIOL PERMEATION THROUGH HUMAN SKIN AND SILASTIC MEMBRANE - EFFECTS OF PROPYLENE-GLYCOL AND SUPERSATURATION
ESTRADIOL PERMEATION THROUGH HUMAN SKIN AND SILASTIC MEMBRANE - EFFECTS OF PROPYLENE-GLYCOL AND SUPERSATURATION
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DOI：
10.1016/0168-3659(95)00062-d
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发表时间：
1995-10-01
影响因子：
10.8
通讯作者：
BARRY, BW
中科院分区：
文献类型：
--
作者：
MEGRAB, NA;WILLIAMS, AC;BARRY, BW
本文研究的经皮渗透增强的一种方法是将经皮给药系统中药物的热力学活性提高到过饱和水平。测定了模型药物雌二醇（OE）在不同浓度丙二醇/水（PG/W）共溶剂体系中的饱和溶解度。利用饱和溶解度曲线，采用混合共溶剂法在PG/W体系中制备了一系列不同饱和倍数的OE过饱和溶液。使用包括羟丙基甲基纤维素（HPMC）、羟丙基纤维素（HPC）、聚乙烯醇（PVA）、聚乙烯吡咯烷酮（PVP）和聚乙二醇4000和8000（PEG 4000和PEG 8000）的抗成核聚合物来稳定过饱和溶液。除了PEG之外，所有PEG都能够延迟OE的结晶，并且聚乙烯吡咯烷酮（MW 40 000）是最有效的。然后使用自动扩散装置检查OE从饱和和过饱和溶液通过人皮肤和硅橡胶膜的传质特性。OE通量从饱和溶液中增加PG浓度。这种增加归因于OE在膜中的溶解度增加。此外，从过饱和溶液中的人角质层和硅橡胶膜的OE的摄取进行了测定。将结果与具有相同PG/W共溶剂组成的饱和溶液的结果进行比较。一般来说，OE通过人体皮肤和硅橡胶膜的吸收和通量都随着饱和度的增加而增加。角质层显示从18倍饱和度的过饱和溶液的摄取增加18.8 +/-4.88倍。OE通量通过人体皮肤从18倍饱和度的溶液中增加了约13倍，在12小时的实验中，从饱和溶液的流量相比。
One approach to transdermal permeation enhancement investigated in this paper is to increase the thermodynamic activity of a drug in the transdermal delivery system to supersaturation levels. Saturated solubilities of the model drug oestradiol (OE) in different concentrations of propylene glycol/water (PG/W) co-solvent systems were determined. Utilising the saturated solubility curve, a series of OE supersaturated solutions at different multiples of saturation in PG/W systems was prepared using a mixed co-solvents method. Antinucleating polymers including hydroxypropylmethylcelluose (HPMC), hydroxypropylcelluose (HPC), polyvinyl alcohol (PVA), polyvinylpynolidone (PVP) and polyethylene glycols, 4000 and 8000 (PEG 4000 and PEG 8000), were used to stabilise the supersaturated solutions. All but the PEGs were able to retard the crystallisation of OE and polyvinylpyrrolidone (MW 40 000) was the most efficient. Mass transport characteristics of OE from saturated and supersaturated solutions through human skin and silastic membranes were then examined using an automated diffusion apparatus. OE flux was enhanced from saturated solutions with increased PG concentration. This increase was attributed to increased OE solubility in the membrane. Also, uptake of OE by human stratum corneum and silastic membrane from supersaturated solution was determined. The results were compared with those from saturated solutions having the same PG/W co-solvent compositions. Generally, both the uptake and flux of OE through both human skin and silastic membrane increased with increasing degree of saturation. Stratum corneum showed an 18.8 +/- 4.88 times increase in uptake from a supersaturated solution of 18 times saturation. OE flux through human skin from a solution of 18 times saturation increased about 13-fold during the 12 h experiment when compared with the flux from saturated solution.