PASSIVE-DRUG DIFFUSION VIA STANDARDIZED SKIN MINI-EROSION - METHODOLOGICAL ASPECTS AND CLINICAL FINDINGS WITH NEW DEVICE

Purpose, To develop a clinical alternative to drug administration by i njection or infusion. Methods. A simple, mechanical device (Cellpatch) enables both the formation of a standardized small epidermal bleb and exposure of the circular base of the bleb to drug. The epidermis is s plit off by suctioning without bleeding or discomfort in a layer super ficial to dermal capillaries and nociceptor nerves. Transdermal invasi vity is thus avoided. Absorption of dextran test drug in aqueous solut ion vs molecular weight (3 kDa-70 kDa) and erosion area (3 kDa, diamet er: 3-10 mm) were studied in healthy volunteers. The feasibility of us ing Morphine cell-patch (cell filled with 20 mg/ml morphine hydrochlor ide, aqueous solution, erosion diameter 6 mm) for post-operative pain relief was studied in two different patient groups; the Cellpatch was removed after 48 hours. Plasma morphine concentrations were determined at intervals. Results. Dextrans of all sizes were efficiently absorbe d transdermally, although absorption decreased with increasing molecul ar weight. The degree of absorption was directly related to the area o f the mini-erosion. There were no sign of dose-dumping even with the l argest erosions. The Cellpatch performed well in the demanding conditi ons of the postoperative unit, and was considered easy to use. Pharmac okinetically, the postoperative morphine delivery was related to that of a continuous infusion, with variability and dose in the same range as a continuous morphine infusion used clinically for providing basal pain relief. There were no bacterial growth in the morphine cells at 4 8 h. Reepithelialization of the erosion was rapid. Conclusions. The fe asibility of administering drugs in a wide size range by passive diffu sion through a standardized skin mini-erosion was demonstrated; the ra te of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven d iffusion of drug into the circulation. As a consequence of the favorab le findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.