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In vitro dermal and transdermal delivery of doxycycline from ethanol/migliol 840 vehicles

Perkins, Nia C. and Heard, Charles Martin 1999. In vitro dermal and transdermal delivery of doxycycline from ethanol/migliol 840 vehicles. International Journal of Pharmaceutics 190 (2) , pp. 155-164. 10.1016/S0378-5173(99)00240-9

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Abstract

This work investigated the feasibility of dermal and transdermal delivery of doxycycline from vehicles containing Migliol 840 (M840) and ethanol. Delivery of the drug via the skin would provide a useful alternative to oral delivery, which has many undesirable side-effects, such as oesophageal ulceration and disturbance of the normal gut flora. Potential applications include malaria prophylaxis, and the treatment of acne vulgaris, Lyme disease and Reiter syndrome. Experiments were performed to determine the permeation of doxycycline across excised full-thickness human skin and heat-separated epidermal membranes from saturated solutions in ethanol, 1:1 and 2:1 ethanol/M840. Unusual burst behaviour was observed using an ethanol vehicle, possibly as a result of the formation of dimers at saturation. Doxycycline permeated to a higher degree from ethanolic vehicles when M840 is present, suggesting that M840 is capable of enhancing the permeation of doxycycline. The flux across full-thickness skin was highest from a 2:1 ethanol:M840 vehicle (2.41 microg cm(-2) h(-1)), sufficient to deliver 282 microg l(-1) using an area of application of 30 cm(2). The data also produced unexpected results in that permeability across heat separated skin was an order of magnitude greater than across full-thickness skin (28.75 microg cm(-2) h(-1) for the 2:1 ethanol:M840 vehicle). Depth profiling indicated that the drug distributed quite evenly throughout the epidermis. The mean amount of doxycycline recovered from the epidermis at the end of a permeation experiment was 458.4 microg ml(-1). This was far higher than the volume of extractable lipid present in the same unit area, approximately 52.3 microg ml(-1) and indicated that a large proportion of the drug must have been located within the proteinaceous domain. The data therefore suggest (1) significant amounts of doxycycline can be administered into and across the skin; (2) M840 is a potentially useful enhancing vehicle; and (3) the transcellular route was of significance.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Doxycycline; Migliol 840; Lyme disease; Malaria; Acne vulgaris; Reiter syndrome; Dermal delivery; Transdermal delivery.
Publisher: Elsevier
ISSN: 0378-5173
Last Modified: 04 Jun 2017 07:44
URI: http://orca.cf.ac.uk/id/eprint/67505

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