Abstract

Cilostazole (CLZ) is an anti-platelet drug that suffers from extensive first pass-metabolism and gastrointestinal side effects. This study aimed to prepare spanlastics for enhancing the transdermal delivery of CLZ to avoid its oral problems. CLZ-loaded spanlastic dispersions were prepared by ethanol injection technique according to a 4¹3¹2¹ full factorial design to investigate the effect of formulation variables on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and the percent of drug released after 2 and 24 h (Q2 and 24 h). Spanlastic-loaded gel of the optimized formula was prepared using hydroxypropyl methylcellulose (HPMC K4M). The optimum formula (F13), constitutes of Span60 and CremophoreRH40 at a weight ratio of 80:20 and distilled water for hydration, had the highest desirability value of (0.841) and exhibited the highest EE% of (69.29 ± 0.29%), PS of (452.7 ± 5.94 nm), ZP of (-32.6 ± 0.4 mV), Q 2 h of (33.28 ± 1.45%) and Q24h of (82.37 ± 1.37. F13 was subjected to ex-vivo permeation study and showed a cumulative amount permeated after 48 h(Q_48h) equal to (750.71 ± 3 μg/cm²) in comparison to the drug suspension which showed Q_48h equal to (190.20 ± 6.3 μg/cm²). Also, F13 showed an increase in the drug flux of (17.84 μg/cm².h) and enhancement ratio(ER) of (5.71 ± 0.1) in comparison to the drug suspension that showed drug flux of (3.12 ± 0.0 μg/cm².h). Spanlastics-loaded gel was subjected to an in-vitro release study compared to(F13) spanlastic dispersion and showed a more sustained release effect. In addition, histopathological studies showed no sign of skin alteration confirming safe delivery through the skin. CLZ showed promising results with high potential to be delivered transdermally.

摘要

西洛他唑 (CLZ) 是一种抗血小板药物，具有广泛的首过代谢和胃肠道副作用。本研究旨在制备弹性塑料以增强 CLZ 的透皮递送以避免其口腔问题。^{根据 4 1} 3 ¹ 2 ¹通过乙醇注射技术制备负载 CLZ 的弹力分散体全因子设计研究配方变量对包封率 (EE%)、粒径 (PS)、zeta 电位 (ZP) 以及 2 小时和 24 小时（Q2 和 24 小时）后药物释放百分比的影响。使用羟丙基甲基纤维素 (HPMC K4M) 制备优化配方的 Spanlastic 加载凝胶。最佳配方（F13），由重量比为 80:20 的 Span60 和 CremophoreRH40 与蒸馏水组成，具有最高的合意度值（0.841）和最高的 EE%（69.29 ± 0.29%），PS (452.7 ± 5.94 nm)、ZP (-32.6 ± 0.4 mV)、Q 2 h (33.28 ± 1.45%) 和 Q24h (82.37 ± 1.37)。F13 进行离体渗透研究并显示累积量48 小时后渗透(Q _48h ) 等于 (750.71 ± 3 μg/cm ²) 与显示 Q _48h等于 (190.20 ± 6.3 μg/cm ² ) 的药物悬浮液相比。此外，与显示药物通量^（ 3.12 ± 0.0 μg/cm ^2.h )。与 (F13) spanlastic 分散体相比，载有 Spanlastics 的凝胶进行了体外释放研究，并显示出更持久的释放效果。此外，组织病理学研究显示没有皮肤改变的迹象，证实通过皮肤安全递送。CLZ 显示出有希望的结果，具有很高的经皮给药潜力。