药学学报, 2016, 51(6): 979-984
引用本文:
梅芬, 曾维东, 万涛, 黄杰伟, 罗双辉, 吴传斌, 徐月红. 醋酸地塞米松微乳的制备及对皮肤渗透性的影响[J]. 药学学报, 2016, 51(6): 979-984.
MEI Fen, ZENG Wei-dong, WAN Tao, HUANG Jie-wei, LUO Shuang-hui, WU Chuan-bin, XU Yue-hong. Dexamethasone acetate microemulsions: formulation and effect on skin permeability[J]. Acta Pharmaceutica Sinica, 2016, 51(6): 979-984.

醋酸地塞米松微乳的制备及对皮肤渗透性的影响
梅芬1, 曾维东2, 万涛2, 黄杰伟1, 罗双辉1, 吴传斌2, 徐月红2
1. 广州白云山医药集团股份有限公司白云山何济公制药厂, 广东 广州 510410;
2. 中山大学药学院, 广东 广州 510006
摘要:
制备水包油型醋酸地塞米松微乳并优化处方,考察其对皮肤渗透性的影响和促进药物透皮的作用。考察醋酸地塞米松在各种脂溶性溶剂、表面活性剂和助表面活性剂中的溶解度;通过伪三元相图和经皮渗透实验,获得最佳微乳处方;采用差示扫描量热法和红外光谱法测定角质层结构在微乳环境下的变化。结果表明,最佳微乳处方为油酸/辛酸癸酸聚乙二醇甘油酯/丙二醇/水(8/45/15/32, w/w),醋酸地塞米松载药量为0.75% (w/w);醋酸地塞米松微乳是混悬液剂型皮肤渗透速率的6.00倍、24 h皮肤滞留量的4.79倍。在微乳环境下,角质层吸热峰和红外吸收特征峰均发生明显变化,表明微乳影响了角质层脂质和角蛋白结构,减弱其屏障功能,从而促进药物经皮渗透。本文制备的醋酸地塞米松微乳具有良好的透皮作用,增渗机制是角质层脂质和角蛋白结构发生改变。微乳可作为有效的醋酸地塞米松经皮给药载体。
关键词:    醋酸地塞米松      微乳      经皮给药      渗透性      角质层     
Dexamethasone acetate microemulsions: formulation and effect on skin permeability
MEI Fen1, ZENG Wei-dong2, WAN Tao2, HUANG Jie-wei1, LUO Shuang-hui1, WU Chuan-bin2, XU Yue-hong2
1. Guangzhou Baiyunshan Hejigong Pharmaceutical Co., Ltd, Guangzhou 510410, China;
2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
Abstract:
The present project was designed to optimize the microemulsion (ME) formulation of oil in water (O/W) for dexamethasone acetate (DA), and examine its impact on DA percutaneous permeation. The saturated solubility of DA in different oils, surfactants and co-surfactants was tested. The ratio of surfactant to co-surfactant was selected by constructing pseudo three phase diagrams to investigate the maximal microemulsion area. In vitro permeation studies of DA from microemulsion and suspension were performed to optimize the formulation further. Differential scanning calorimetry (DSC) and attenuated total reflection flourier transformed infrared spectroscopy (ATR-FTIR) were performed to investigate the mechanism of microemulsion action on skin. The optimized formulation was composed of oleic acid/Labrasol/propylene glycol/water with 8/45/15/32(w/w), and the DA loading was 0.75% (w/w). The permeation enhancement of microemusion was 6.00-fold as that of suspension, and the DA from microemulsion retained in the skin was 4.79-fold as that of suspension. DSC and ATR-FTIR results suggested that microemulsion could affect the intercellular lipid lamellae and keratin of the stratum corneum. The barrier function of stratum corneum was disordered by the microemulsion so that the dermal drug delivery was enhanced. Therefore, the optimized microemulsion enhanced DA percutaneous permeation significantly through the interaction of microemulsion with skin, microemulsion is a promising approach for DA percutaneous delivery.
Key words:    dexamethasone acetate    microemulsion    percutaneous delivery    permeability    stratum corneum   
收稿日期: 2015-12-16
DOI: 10.16438/j.0513-4870.2015-1154
基金项目: 国家自然科学基金资助项目(81073066,81473358).
通讯作者: 徐月红,Tel/Fax:86-20-39943119,E-mail:lssxyh@mail.sysu.edu.cn
Email: lssxyh@mail.sysu.edu.cn
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