Liu Nannan, Song Wenting, Song Tian, Fang Liang
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China.
AAPS PharmSciTech. 2016 Apr;17(2):262-71. doi: 10.1208/s12249-015-0342-9. Epub 2015 Jun 13.
The aim of this study was to design a novel felbinac (FEL) patch with significantly higher (P < 0.05) skin permeation amount than the commercial product SELTOUCH® using ion-pair and chemical enhancer strategy, overcoming the disadvantage of the large application area of SELTOUCH®. Six complexes of FEL with organic amines diethylamine (DEA), triethylamine (TEA), N-(2'-hydroxy-ethanol)-piperdine (HEPP), monoethanolamine (MEtA), diethanolamine (DEtA), and triethanolamine (TEtA) were prepared by ion-pair interaction, and their formation were confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), infared spectroscopy (IR), and proton nuclear magnetic resonance spectroscopy ((1)H-NMR). Subsequently, the effect of ion-pair complexes and chemical enhancers were investigated through in vitro and in vivo experiments using rabbit abdominal skin. Results showed that FEL-TEA was the most potential candidate both in isopropyl palmitate (IPP) solution and transdermal patches. Combining use of 10% N-dodecylazepan-2-one (Azone), the optimized FEL-TEA patch achieved a flux of 18.29 ± 2.59 μg/cm(2)/h, which was twice the amount of the product SELTOUCH® (J = 9.18 ± 1.26 μg/cm(2)/h). Similarly, the area under the concentration curve from time 0 to time t (AUC0-t ) in FEL-TEA patch group (15.94 ± 3.58 h.μg/mL) was also twice as that in SELTOUCH® group (7.31 ± 1.16 h.μg/mL). Furthermore, the in vitro skin permeation results of FEL-TEA patch was found to have a good correlation with the in vivo absorption results in rabbit. These findings indicated that a combination of ion-pair and chemical enhancer strategy could be useful in developing a novel transdermal patch of FEL.
本研究的目的是采用离子对和化学增强剂策略设计一种新型非甾体抗炎药（FEL）贴剂，其皮肤渗透量显著高于市售产品SELTOUCH®（P < 0.05），克服SELTOUCH®应用面积大的缺点。通过离子对相互作用制备了FEL与有机胺二乙胺（DEA）、三乙胺（TEA）、N-（2'-羟基乙醇）哌啶（HEPP）、单乙醇胺（MEtA）、二乙醇胺（DEtA）和三乙醇胺（TEtA）的六种复合物，并通过差示扫描量热法（DSC）、粉末X射线衍射（pXRD）、红外光谱（IR）和质子核磁共振光谱（（1）H-NMR）确认了它们的形成。随后，通过使用兔腹部皮肤的体外和体内实验研究了离子对复合物和化学增强剂的作用。结果表明，FEL-TEA在棕榈酸异丙酯（IPP）溶液和透皮贴剂中都是最有潜力的候选物。结合使用10% N-十二烷基氮杂环庚烷-2-酮（氮酮），优化后的FEL-TEA贴剂通量达到18.29±2.59 μg/cm(2)/h，是产品SELTOUCH®（J = 9.18±1.26 μg/cm(2)/h）的两倍。同样，FEL-TEA贴剂组从时间0到时间t的浓度曲线下面积（AUC0-t）（15.94±3.58 h.μg/mL）也是SELTOUCH®组（7.31±1.16 h.μg/mL）的两倍。此外，发现FEL-TEA贴剂的体外皮肤渗透结果与兔体内吸收结果具有良好的相关性。这些发现表明，离子对和化学增强剂策略的组合可用于开发新型FEL透皮贴剂。
