Effect of tretinoin inclusion in dimethyl-beta-cyclodextrins on release rate from a hydrogel formulation
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The aim of this work was to study the release, permeation and skin retention profiles of 0.05% tretinoin hydrogel formulations in which tretinoin was in free form or complexed with dimethyl-beta-cyclodextrin in a stoichiometry of 1:4. Theoretically, this complexation will mainly allow to: overcome drug’s low water solubility and low stability; enhance the drug permeation by promoting skin absorption and alleviate drug inducing local irritation. In vitro release, permeation and skin retention tests were performed in both formulations in order to compare the main advantages of this complexation. The influence of the thermodynamic activity on the drug release profile was also investigated. This study proved that tretinoin inclusion complexes formulation with excess of cyclodextrins had better release profile than the free tretinoin formulation. It was concluded that in this study, thermodynamic activity was not the driving force for the release rate improvement observed with cyclodextrins. Probably, this improvement was due to the increased availability of tretinoin near the membrane surface. In fact, the percentage of total drug that had been retained in the skin was 0.41 ± 0.08% for complexed tretinoin gel and 0.17 ± 0.04% for the free tretinoin gel.
KeywordsTretinoin Dimethyl-beta-cyclodextrin In vitro drug release/permeation and skin retention Thermodynamic activity
We thank to Marta Machado from iMed for technical support; to Allergisa, S. Paulo, Campinas, Brazil for the performance of the active retention studies and to Dr. John Pugh from the University of Wales, College of Cardiff for the Modelling Enhancer Activity calculations.
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