RESUMO
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.
RESUMO
The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.