Department of Pharmaceutics, College of Pharmaceutical Sciences, Berhampur, Orissa, India.
Drug Dev Ind Pharm. 2011 Apr;37(4):465-74. doi: 10.3109/03639045.2010.522192.
A nonoral alternative such as transdermal system is desired to improve bioavailability and to maintain a constant and prolonged drug level with reduced frequency of dosing.
The objective of the investigation is to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the influence of chemical permeation enhancers (CPEs) on the percutaneous permeation pattern.
A D-optimal mixture design was used to study the influence of CPE with oleic acid (OA), lauric acid, and propylene glycol (PG) as mixture components. The influence of chemical enhancers on skin permeation was compared using one-way analysis of variance followed by multiple comparison analysis. Criterion of desirability was used to optimize the therapeutic system. Preclinical studies in rabbits were also carried out to establish an ex vivo-in vivo correlation (EVIVC).
The drug permeation pattern suggested Higuchian diffusion as predominant mode followed by case II to super case II transport as drug transport mechanism. The optimized formulation was obtained using 5% (w/w) CPE consisting of a blend of 62.41% OA and 37.59% PG. About twofold increase in alfuzosin permeation was achieved with the optimized transdermal patch. An approximate linear EVIVC was established (R(2) = 0.971).
The optimized blend of enhancers could improve skin permeation parameters. A higher extent of in vivo skin permeation compared with cadaver skin permeation may be due to more permeable nature of rabbit skin.
The investigations suggest an effective alternative delivery strategy such as transdermal systems for alfuzosin hydrochloride.
为了提高生物利用度并保持恒定且延长的药物水平，减少给药频率，需要一种非口服替代方案，如透皮系统。
本研究旨在开发盐酸阿夫唑嗪的透皮治疗系统，并研究化学渗透增强剂（CPE）对经皮渗透模式的影响。
采用 D-最优混合设计研究以油酸（OA）、月桂酸和丙二醇（PG）为混合物成分的 CPE 的影响。使用单向方差分析（ANOVA）和多重比较分析比较化学增强剂对皮肤渗透的影响。使用适宜度标准优化治疗系统。还在兔子中进行了临床前研究以建立体外-体内相关性（EVIVC）。
药物渗透模式表明，Higuchi 扩散是主要模式，随后是第二案例至超级第二案例传输作为药物传输机制。使用包含 62.41%OA 和 37.59%PG 的混合 5%（w/w）CPE 获得了优化的制剂。优化的透皮贴剂使阿夫唑嗪的渗透增加了约两倍。建立了近似线性的 EVIVC（R²=0.971）。
优化的增强剂混合物可以改善皮肤渗透参数。与尸体皮肤渗透相比，体内皮肤渗透程度更高可能是由于兔子皮肤的渗透性更高。
这些研究表明，盐酸阿夫唑嗪的透皮系统是一种有效的替代给药策略。
