这项工作的目的是在体外和离体表征Durogesic和两种生物等效通用产品的性能,通过评价:(a)芬太尼释放;(b)芬太尼通过猪皮肤的渗透和(c)芬太尼的提取容易性。研究的其他特征是温度和皮肤完整性的影响,单独或组合应用,检查可能的协同作用。根据新的指南,这两个通用补丁的结果等同于发起者。然而,同样的数据以不同的方式报告,即考虑整个贴剂在施用时间内渗透的药物总量,突出显示补丁之间的差异。进行的额外测试表明,皮肤完整性并不代表芬太尼渗透穿过皮肤的障碍,无论修补程序的类型和复杂性如何。温度的影响导致三个补丁中的两个至关重要,可能是由于不同的成分和不同的结构。皮肤损伤和升高的温度的组合没有产生协同作用。芬太尼的提取对于不同的产品是不同的,并且根据使用的条件而变化。本研究报告的结果强调了贴剂成分和复杂性对芬太尼提取的影响,释放和皮肤渗透,特别是在可能是关键的条件下,如温度升高。特别是,关键变量的影响,如皮肤完整性和温度,在开发新的或新的通用补丁和新的判别式测试应该被解决。
The aim of this work was to characterize in vitro and ex vivo the performances of Durogesic and of two bioequivalent generic products, by evaluating: (a) fentanyl release; (b) fentanyl permeation across porcine skin and (c) fentanyl ease of extraction. Additional characteristics studied are the effect of temperature and skin integrity, applied individually or combined, to check a possible synergism. The two generic patches resulted equivalent to the originator according to the new
Guideline. Nevertheless, the same data reported in a different way, i.e. considering the total amount of drug permeated from the whole patch over the application time, highlight differences among the patches. The additional tests performed showed that skin integrity does not represent a barrier for fentanyl permeation across the skin, regardless of the type and complexity of the patch. The effect of temperature resulted critical for two out of three patches, probably due to the different composition and to the different structure. The combination of skin damage and elevated temperature did not produce a synergistic effect. Fentanyl extraction was different for the different products and variable according to the conditions used. The results reported in the present work underline the influence of patch composition and complexity on fentanyl extraction, release and skin permeation, in particular in conditions that can be critical, such as elevated temperature. In particular, the effect of critical variables, such as skin integrity and temperature, should be addressed to in the development of a new or new generic patch and new discriminant tests should be developed.