In Vitro, Ex Vivo, and In Vivo Evaluation of the Effect of Saturated Fat Acid Chain Length on the Transdermal Behavior of Ibuprofen-Loaded Microemulsions
In Vitro, Ex Vivo, and In Vivo Evaluation of the Effect of Saturated Fat Acid Chain Length on the Transdermal Behavior of Ibuprofen-Loaded Microemulsions
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DOI：
10.1002/jps.23958
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发表时间：
2014-06-01
影响因子：
3.8
通讯作者：
Fang, Xiaoling
中科院分区：
文献类型：
--
作者：
Ren, Qiuyue;Deng, Chunli;Fang, Xiaoling
在本研究中，在体外、离体和体内评估了油相中饱和脂肪酸（FA）链长对布洛芬（IBU）负载的透皮微乳（ME）行为的影响。经过实验优化后，选择了长链（LFA）、中链（MFA）和短链（SFA）三种油，Cremophor RH40（表面活性剂）和Transcutol P（辅助表面活性剂）。对 ME 的理化性质进行了表征，包括 IBU 在赋形剂中的溶解度、伪三元相图结构、粒径、zeta 电位、粘度和稳定性。使用 Franz 细胞系统的 IBUex 体内渗透通量和残留量按以下顺序发生：基于 MFA 的 ME > 基于 LFA 的 ME > 基于 SFA 的 ME，这与共焦扫描激光显微镜研究和体内保留研究的结果具有良好的相关性。体外细胞毒性研究和差示扫描量热法测量的皮肤刺激试验结果按以下顺序排列：基于LFA的ME>基于MFA的ME>基于SFA的ME。此外，基于 MFA 的 ME 在所有治疗组中具有最高的镇痛活性。 MFA 被发现是 IBU 负载透皮 ME 的最佳油相，具有适当的 FA 链长度，具有优异的理化性质、低毒性和良好的渗透性。 (c) 2014 年 Wiley periodicals, Inc. 和美国药剂师协会 J Pharm Sci
In this study, the effect of the saturated fatty acid (FA) chain length in the oil phase on the behavior of Ibuprofen (IBU)-loaded transdermal microemulsion (ME) was evaluated in vitro, ex vivo, and in vivo. Three oils classified as long (LFA), medium (MFA), and short (SFA) chain length oils, Cremophor RH40 (surfactant) and Transcutol P (cosurfactant) were selected after experimental optimization. The physicochemical properties of ME were characterized, including IBU solubility in excipients, pseudo-ternary phase diagram construction, particle size, zeta potential, viscosity, and stability. Permeation flux and residual amount of IBUex vivo using Franz cell system occurred in the following order: MFA-based ME > LFA-based ME > SFA-based ME, which correlated well with the results of confocal scanning laser microscopy study and the in vivo retention study. The results of in vitro cytotoxicity study and skin irritation tests measured by differential scanning calorimetry were ranked in the following order: LFA-based ME > MFA-based ME > SFA-based ME. Moreover, MFA-based ME has the highest analgesic activity among all the treatment groups. MFA was found to be an optimal oil phase with appropriate FA chain length for IBU-loaded transdermal ME, which exhibited excellent physicochemical properties, low toxicity, and good permeability profile. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci