デュルケーム社会理論における「意味｣の問題

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.