Meyer Stefanie, Heinsohn Guido, Wolber Rainer, Pörtner Ralf, Nierle Jens
a Research & Development , Beiersdorf AG , Hamburg , Germany and.
b Institute of Bioprocess and Biosystems Engineering , Hamburg University of Technology , Hamburg , Germany.
Drug Deliv. 2015 Dec;22(8):1103-1110. doi: 10.3109/10717544.2014.889778. Epub 2014 Mar 3.
Release from a transdermal drug delivery system (TDDS) can either be controlled by diffusion in the adhesive, by diffusion processes in the stratum corneum of the skin or a combination of both. In this study, diffusion processes in monolithic type TDDS were investigated using confocal Raman microscopy. An acrylic adhesive (Duro-Tak 180-129a), a rubber adhesive (Duro-Tak H1540) and a silicone adhesive (BIO-PSA 7-4202) were used. Skin permeation of the model drug Paeonol from these adhesives was investigated. Release studies on porcine cadaver skin were carried out. Solubility of Paeonol in the different adhesives was measured. Diffusion coefficients of the drug in the TDDSs were calculated from confocal Raman depth scans, the diffusion coefficient in the stratum corneum was calculated using tape stripping. Solubility of Paeonol in the acrylic adhesive was the highest with 30 g/L among the tested systems. Paeonol had a solubility of 6 and 9 g/L in the silicone and rubber based system. Diffusion coefficient rank order was BIO-PSA 7-4204 > Duro-Tak 180-129a > Duro-Tak H1540. Release on porcine cadaver skin from the silicone was the highest followed by the rubber and the acrylic adhesive. During release studies on porcine skin with Duro-Tak H1540 no concentration gradient of Paeonol could be monitored in the Raman depth profiles, whereas in the stratum corneum an apparent diffusion gradient was detectable. Solubility of a drug in the adhesive dominated the release properties, high-diffusion coefficients of drugs in adhesives do not necessarily lead to high release rates from adhesives.
从透皮给药系统（TDDS）释放药物可以通过在粘合剂中的扩散、皮肤角质层中的扩散过程或两者的结合来控制。在本研究中，使用共聚焦拉曼显微镜研究了整体型TDDS中的扩散过程。使用了丙烯酸粘合剂（Duro-Tak 180-129a）、橡胶粘合剂（Duro-Tak H1540）和硅酮粘合剂（BIO-PSA 7-4202）。研究了模型药物丹皮酚从这些粘合剂中的皮肤渗透情况，并在猪尸体皮肤上进行了释放研究，测量了丹皮酚在不同粘合剂中的溶解度。根据共聚焦拉曼深度扫描计算药物在TDDS中的扩散系数，使用胶带剥离法计算角质层中的扩散系数。在测试系统中，丹皮酚在丙烯酸粘合剂中的溶解度最高，为30 g/L。丹皮酚在硅酮和橡胶基系统中的溶解度分别为6 g/L和9 g/L。扩散系数的排序为BIO-PSA 7-4204＞Duro-Tak 180-129a＞Duro-Tak H1540。硅酮粘合剂在猪尸体皮肤上的释放量最高，其次是橡胶粘合剂和丙烯酸粘合剂。在用Duro-Tak H1540对猪皮肤进行释放研究期间，在拉曼深度剖面图中未监测到丹皮酚的浓度梯度，而在角质层中可检测到明显的扩散梯度。药物在粘合剂中的溶解度主导了释放特性，药物在粘合剂中的高扩散系数不一定导致从粘合剂中的高释放率。
