Confocal Raman investigation of diffusion processes in monolithic type transdermal drug delivery systems

Abstract

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 7-42044Duro-Tak 180-129a4Duro-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.

Novel aspects of Raman spectroscopy in skin research

“…Likewise, it is used to evaluate potentially hazardous permeants in toxicological studies. For these tasks, different membranes are used: human skin in vivo, 103 human skin ex vivo, 104,105 in vitro skin substitutes 75 and porcine skin 52,54,106,107,108,109 . Rodent skin 110 is rarely due to its inherent differences to human skin.…”

“…For these tasks, different membranes are used: human skin in vivo, 103 human skin ex vivo, 104,105 in vitro skin substitutes 75 and porcine skin. 52,54,106,107,108,109 Rodent skin 110 is rarely due to its inherent differences to human skin. Caffeine, 52,106,109,111,112,113 lidocaine, 104 procaine, 107,114 tetracaine, 115 salicylic acid, 113 ibuprofen, 103 flufenamic acid, 105 imiquimod, 116 trans-retinol, 117,118 resorcinol, 75 niacinamide, 119 sulfathiazole sodium, 54 triamcinolone acetonide 120 and oxaprozin are among the most investigated permeants in the CRS penetration studies.…”