Wang Zheng, Mu Hong-Jie, Zhang Xue-Mei, Ma Peng-Kai, Lian Sheng-Nan, Zhang Feng-Pu, Chu Sheng-Ying, Zhang Wen-Wen, Wang Ai-Ping, Wang Wen-Yan, Sun Kao-Xiang
School of Pharmacy, Yantai University, Yantai, Shandong Province, People's Republic of China.
School of Pharmacy, Yantai University, Yantai, Shandong Province, People's Republic of China ; State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People's Republic of China.
Int J Nanomedicine. 2015 Jan 14;10:633-44. doi: 10.2147/IJN.S74079. eCollection 2015.
Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats).
The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions.
Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies.
The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil(®), 13.44% Cremophor(®) RH40, 6.72% Labrasol(®), and 5.04% Transcutol(®) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro(®)). The microemulsion gel irritated the skin less than Neupro.
A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.
罗替戈汀是一种强效且具有选择性的D1、D2和D3多巴胺能受体激动剂。由于广泛的首过效应，其口服生物利用度极低（在大鼠中约为0.5%）。
本研究旨在开发一种基于微乳的水凝胶，用于罗替戈汀的经皮给药，以降低用药部位反应。
构建伪三元相图以确定水包油（o/w）型微乳区域。采用中心复合设计来辅助伪三元相图，并选择在24小时内具有最佳罗替戈汀渗透量的均匀稳定微乳。使用Franz扩散池进行体外皮肤渗透实验，以比较载有罗替戈汀的微乳与油溶液中的罗替戈汀。将优化后的配方用于制备基于微乳的水凝胶，并进行生物利用度和皮肤刺激性研究。
与油溶液中的罗替戈汀相比，所选载有罗替戈汀的微乳配方具有更高的通量和渗透系数。最佳微乳包含68%的水、6.8%的Labrafil(®)、13.44%的Cremophor(®) RH40、6.72%的Labrasol(®)和5.04%的Transcutol(®) HP；载药率为2%。为形成微乳凝胶，向微乳中添加1%的卡波姆1342。相对于市售罗替戈汀贴剂（Neupro(®)），载有罗替戈汀的微乳凝胶的生物利用度为105.76%±20.52%。微乳凝胶对皮肤的刺激性小于Neupro。
成功开发了一种基于罗替戈汀微乳的水凝胶，并确定了药物递送的最佳配方。该产品可提高患者依从性，具有广阔的市场前景。
