Reconstructed skin equivalents for assessing percutaneous drug absorption from pharmaceutical formulations.
2001
: Excised human skin has so far been considered to be one of the most suitable in vitro methods to evaluate the penetration of dermatologically applied substances. The limited supply and the relatively high donor variability stimulated many research groups to use animal skin as a substitute for human skin. Since nowadays reconstructed skin equivalents are commercially available, we examined these cultures for their suitability as a percutaneous absorption model for different pharmaceutical formulations. One such equivalent is EpiDerm (EPI-606, MatTek corporation, Ashland Massachusetts) which was investigated using the lipophilic model drug flufenamic acid. Permeation studies with the Franz diffusion cell were undertaken to evaluate the model for the establishment of a new in vitro method to study the percutaneous absorption of different dosage forms. The drug was applied in two pharmaceutical formulations to the intact surface of the skin disk: dissolved in wool alcohol ointment (0.1125 %), and dissolved in Soerensen phosphate buffer pH 7.4 (0.1125% solution). HPLC was used for the analysis of drug content. It was shown that the model forms a barrier towards diffusion by comparing the permeation across the tissue-free inserts to the equivalents. Flux values were calculated and the permeation across the skin equivalent from the solution was noted to be almost forty times higher than from the ointment. Two different batches of the skin equivalent showed no statistically significant difference. Finally the permeability of the reconstructed skin was compared to human epidermis, and a five times higher flux value was found for the skin equivalent model. Our results suggest that reconstructed skin equivalents based on human keratinocytes have potential as a pharmaceutical test system to study dermal drug transport from topical formulations.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
30
Citations
NaN
KQI