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Clinical Trial
. 2003 Dec 18:3:5.
doi: 10.1186/1471-5945-3-5.

Solvent effects in permeation assessed in vivo by skin surface biopsy

Catarina Rosado  1 , Luis Monteiro Rodrigues
Affiliations
Clinical Trial

Solvent effects in permeation assessed in vivo by skin surface biopsy

Catarina Rosado et al. BMC Dermatol. .

Abstract

Background: Transdermal drug delivery has become an important means of drug administration. It presents numerous advantages but it is still limited by the small number of drugs with a suitable profile. The use of solvents that affect the skin barrier function is one of the classic strategies of penetration enhancement. Some of these solvents have well characterised actions on the stratum corneum, but the majority are still selected using empirical criteria. The objective of this work was to conduct a systematic study on the ability to affect skin permeation of solvents commonly used in transdermal formulations. An innovative methodology in this area was employed, consisting of the combination of skin surface biopsy with colorimetry.

Methods: The study compared in vivo differences in the permeation of a hydrophilic (methylene blue) and a lipophilic (Sudan III) dye, after treatment of the skin with different vehicles. Consecutive skin surface biopsies of each site were taken and the cumulative amounts of the dyes in the stripped stratum corneum were measured by reflectance colourimetry.

Results: Results indicate that the amount of methylene blue present in the stratum corneum varied significantly with different skin pre-treatments. Some solvents provided a 1.5 fold penetration enhancement but others decreased by almost half the permeation of the dye. The permeation of Sudan III was less significantly affected by solvent pre-treatment.

Conclusions: This study has only superficially explored the potential of the combination of skin surface biopsy and colourimetry, but the encouraging results obtained confirm that the methodology can be extended to the study of more complex formulations.

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Figures

Figure 1
Figure 1
Cumulative a* values (arbitrary units) obtained after application of Sudan III and different solvent treatments (mean ± SD) IPM – isopropyl myristate; oct/PG – octanol: propylene glycol 1:1; AO/PG – oleic acid: propylene glycol 1:1; PG – propylene glycol. Statistical differences between pre-treatment and control results represented by * (p < 0.01), ** (p < 0.05) and NS (no statistical difference)
Figure 2
Figure 2
Enhancement ratio of Sudan III provided by different solvent treatments (mean ± SD) IPM – isopropyl myristate; oct/PG – octanol: propylene glycol 1:1; AO/PG – oleic acid: propylene glycol 1:1; PG – propylene glycol.
Figure 3
Figure 3
Cumulative |b|* values (arbitrary units) obtained after application of methylene blue and different solvent treatments (mean ± SD) IPM – isopropyl myristate; oct/PG – octanol: propylene glycol 1:1; AO/PG – oleic acid: propylene glycol 1:1; PG – propylene glycol. Statistical differences between pre-treatment and control results represented by * (p < 0.01), ** (p < 0.05) and NS (no statistical difference)
Figure 4
Figure 4
Enhancement ratio of methylene blue provided by different solvent treatments (mean ± SD) IPM – isopropyl myristate; oct/PG – octanol: propylene glycol 1:1; AO/PG – oleic acid: propylene glycol 1:1; PG – propylene glycol.
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