复方体外培育牛黄微乳凝胶的经皮渗透研究

Study on Transdermal Permeation of Compound Cultivated Calculus Bovis Microemulsion Gel in vitro

目的研究不同体外培育牛黄浓度复方微乳凝胶的经皮渗透行为,以及透皮成分之间的相互影响。方法不同药物浓度复方体外培育牛黄微乳凝胶分别进行体外经皮渗透实验,采用高效液相色谱法检测透皮接收液中指标成分盐酸小檗碱和丹皮酚含量,以零级、一级、Higuchi动力学方程对结果进行数据拟合,阐明载药量对制剂经皮渗透速率的影响及其递变规律,并采用相同方法考察两个指标成分单用与合用透皮行为的差异。结果在考察药物浓度范围,复方体外培育牛黄微乳凝胶中盐酸小檗碱成分经皮渗透参数均以零级动力学方程拟合为优,表明该成分透过皮肤是一个被动扩散过程,单位时间透皮量与基质药物浓度呈正比,且Q-t关系可用Ficks扩散定律来描述。而丹皮酚成分经皮渗透参数则均以Higuchi动力学方程拟合为优,表明在此浓度范围内丹皮酚从凝胶基质骨架中释放量遵循单位面积释放量与时间的平方根成正比的规律,但基质药物浓度增加与单位时间透皮量提高不呈比例。盐酸小檗碱单一成分制剂16 h内累积透皮量显著大于复方制剂(P<0.05),而丹皮酚单一成分制剂与复方制剂在考察时间内累积透皮量差异较小。结论虽然提高体外培育牛黄浓度可以不同程度增加复方体外培育牛黄微乳凝胶中盐酸小檗碱与丹皮酚的经皮渗透速率,但仍存在影响盐酸小檗碱释放或透皮的不利因素,需要加以改进与克服。

Objective To study the transdermal permeability of compound cultivated calculus bovis microemulsion gel prepared with different concentrations of drugs and the interaction among transdermal components. Methods In vitro transdermal permeation experiments were carried out to test compound cultivated calculus bovis microemulsion gels with different drug concentrations.The concentrations of berberine hydrochloride and paeonol in the transdermal receiving solution were determined by high performance liquid chromatography, and the results were fitted with zero order, first order, and Higuchi dynamic equations.The effect of drug loading amount on the transdermal rates and the differentiation pattern were elucidated.The same method was also used to examine the differences in transdermal behavior between the two single components alone and in combination. Results Within the range of testing drug concentrations, the permeation parameters of berberine hydrochloride in compound calculus bovis microemulsion gel were best fitted with zero-order kinetic equation, indicating that the component passed through the skin via a passive diffusion process.The amount of skin permeation per unit time was proportional to the concentration of the matrix drug, and the Q-t relationship could be described by the Ficks diffusion law.However, the transdermal permeation parameters of paeonol were best fitted by Higuchi kinetic equation, indicating that the release amount of paeonol per unit area from the gel matrix was proportional to the square root of the time.But the increase of matrix drug concentration was not proportional to the increase of transdermal amount per unit time.The cumulative transdermal amount of single component preparation of berberine hydrochloride in 16 hours was significantly higher than that of the compound preparation(P<0.05), while the cumulative transdermal amount of single component preparation of paeonol and the compound preparation had little difference in the examination period. Conclusion Although increasing the drugs concentration could increase the transdermal permeation rate of berberine hydrochloride and paeonol in calculus bovis microemulsion gel, there are still some adverse factors that may affect the release and penetration of berberine hydrochloride.Thus, further improvements are needed to overcome these problems.