Passive drug diffusion via standardized skin mini-erosion; methodological aspects and clinical findings with new device.
OBJECTIVE
To develop a clinical alternative to drug administration by injection 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 split off by suctioning without bleeding or discomfort in a layer superficial to dermal capillaries and nociceptor nerves. Transdermal invasivity is thus avoided. Absorption of dextran test drug in aqueous solution vs molecular weight (3 kDa-70 kDa) and erosion area (3 kDa, diameter: 3-10 mm) were studied in healthy volunteers. The feasibility of using Morphine cellpatch (cell filled with 20 mg/ml morphine hydrochloride, 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 absorbed transdermally, although absorption decreased with increasing molecular weight. The degree of absorption was directly related to the area of the mini-erosion. There were no sign of dose-dumping even with the largest erosions. The Cellpatch performed well in the demanding conditions of the postoperative unit, and was considered easy to use. Pharmacokinetically, 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 48 h. Reepithelialization of the erosion was rapid.


CONCLUSIONS
The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven diffusion of drug into the circulation. As a consequence of the favorable findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.
Svedman
P
P
Department of Plastic and Reconstructive Surgery, Lund University, University Hospital, Malmö, Sweden.
Lundin
S
S
Höglund
P
P
Hammarlund
C
C
Malmros
C
C
Pantzar
N
N
D000279:Administration, Cutaneous; D000328:Adult; D003911:Dextrans / Q000493:pharmacokinetics*; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010146:Pain / Q000097:blood / Q000188:drug therapy; D012869:Skin Absorption; D013396:Suction
D003911:Dextrans; D009020:Morphine