In vitro evaluation of percutaneous absorption of an acyclovir product using intact and tape-stripped human skin.
OBJECTIVE
To evaluate the use of a flow-through diffusion cell system to assess the absorption and penetration characteristics of drug (acyclovir) products.


METHODS
In vitro studies were performed to assess the absorption/penetration of acyclovir using a flow-through diffusion cell system with human skin sections obtained from 19 healthy women following mammoplasty. The skin sections, 200-400 microm thick, were prepared using a dermatome. Acyclovir ointment (approximately 10 mg) spiked with (3)H-labelled acyclovir was applied onto the stratum corneum/epidermis side. The skin sections were continually perfused on the dermis side with sterilized culture medium, Buffered Hanks' Balanced Salt Solution, saturated with a CO(2)/O(2) (5/95%).


RESULTS
After 24 hours, the percentages of acyclovir-derived radioactivity (based on dose applied) in different components were as follows: stratum corneum (SC), 0.20+0.28; viable skin (VS), 0.40+0.38; effluent fluid (EF), 0.25+0.53. A second set of experiments was performed using tape stripped (10X) skin sections. Levels of acyclovir-derived radioactivity were VS, 1.21+1.43 and EF, 2.65+2.61, which were threefold higher (p < 0.05) for VS and elevenfold higher (p < 0.05) for EF compared to the results obtained with the intact skin sections.


CONCLUSIONS
The SC is the main barrier layer for the penetration of acyclovir through human skin. The use of the flow-through diffusion cell system provides an appropriate in vitro model to assess the absorption/penetration of acyclovir through human skin layers and therefore can potentially be used for dermal formulation characterization and development.
Qureshi
S A
SA
Therapeutic Products Directorate vertical line(PL#2202C1), Health Canada, Ottawa, Ontario, Canada. Saeed_qureshi@hc-sc.gc.ca
Jiang
M
M
Midha
K K
KK
Skelly
J P
JP
D000212:Acyclovir / Q000378:metabolism / Q000493:pharmacokinetics*; D000328:Adult; D000998:Antiviral Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001940:Breast; D004058:Diffusion; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability; D012867:Skin / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D012869:Skin Absorption
D000998:Antiviral Agents; D000212:Acyclovir