Abstract：
Trazodone is a triazolpyridine derivative approved for the treatment of depression, and currently marketed as oral formulations. The transdermal administration of this drug could reduce side effects, related to peak plasma concentration, and improve patient adherence due to a reduced administration frequency. The aims of this work were: (a) the evaluation of the effect of pH vehicle and permeation enhancers on trazodone permeability across porcine skin ex-vivo; (b) the development and optimization of a transdermal drug delivery system containing trazodone hydrochloride. From the results obtained, it was found that the effect of pH of the vehicle on the permeation of trazodone across the skin is quite complex, because it influences both solubility and partitioning and that the presence of fatty acids in the vehicle has a notable effect on permeation (the enhancement factor obtained was approx. 100). For both the fatty acid selected (oleic and lauric) a parabolic relationship between the transdermal flux and the concentration was found, with an optimum activity in the range 2-3 %. In the second part of the work, different patches were prepared and tested ex-vivo. Overall, the results obtained seem to highlight that drug loading, rather than the components of the adhesive matrix, plays the most relevant role for the permeation of trazodone. The addition of lauric acid, which produced a considerable enhancement in solution, was not effective when included in the patch. The obtained data are promising although probably not clinically relevant for the treatment of depression, but might be interesting for the treatment of insomnia and anxiety disorder, which require much lower doses.
摘要：
曲唑酮是被批准用于治疗抑郁症的三唑吡啶衍生物，目前作为口服制剂销售。这种药物的透皮给药可以减少副作用，与血浆峰值浓度有关，并由于减少了给药频率而提高了患者的依从性。这项工作的目的是：a）评估pH媒介物和渗透促进剂对离体猪皮肤中曲唑酮渗透性的影响；b）开发和优化含有盐酸曲唑酮的透皮给药系统。从获得的结果来看，结果发现，媒介物的pH值对曲唑酮通过皮肤的渗透的影响是相当复杂的，因为它影响溶解度和分配，并且载体中脂肪酸的存在对渗透具有显着影响（获得的增强因子约为。100).对于所选择的脂肪酸（油酸和月桂酸），发现透皮通量与浓度之间存在抛物线关系。最佳活性在2-3%的范围内。在工作的第二部分，制备不同的贴剂并进行离体测试.总的来说,获得的结果似乎突出了药物装载，而不是粘合剂基质的成分，对曲唑酮的渗透起着最相关的作用。月桂酸的加入，这在解决方案上产生了相当大的增强，当包含在贴片中时无效。获得的数据是有希望的，尽管可能与抑郁症的治疗没有临床相关性，但对于治疗失眠和焦虑症可能很有趣，这需要更低的剂量。
