Abstract
This is the first study on the modeling of the controlled release of the estimated antioxidants (flavonoids or flavonolignans) from β-cyclodextrin (β-CD)/hydrophilic vegetable extract complexes and the modeling of transdermal pharmaceutical formulations based on these complexes using an overall estimation by the spectrophotometric method. The Korsmeyer-Peppas model was chosen for evaluating the release mechanisms. β-CD/chamomile (Matricaria chamomilla L., Asteraceae) ethanolic extract and β-CD/milk thistle (Silybum marianum L., Asteraceae) ethanolic extract complexes were obtained by the co-crystallization method with good recovering yields of 55-76%, slightly lower than for β-CD/silibinin or silymarin complexes (~87%). According to differential scanning calorimetry (DSC) and Karl Fischer water titration (KFT), the thermal stability of complexes is similar to β-CD hydrate while the hydration water content is lower, revealing the formation of molecular inclusion complexes. In the Korsmeyer-Peppas model, β-CD/M. chamomilla flower extract complexes reveal Case II transport mechanisms, while the corresponding complexes with leaf extracts indicate non-Fickian diffusion for the controlled release of antioxidants in ethanol 60 and 96%. The same non-Fickian diffusion was revealed by β-CD/S. marianum extract and β-CD/silibinin complexes. On the contrary, almost all model transdermal pharmaceutical formulations based on β-CD/M. chamomilla extract complexes and all those based on β-CD/S. marianum extract complexes revealed non-Fickian diffusion for the antioxidant release. These results indicate that H-bonding is mainly involved in the diffusion of antioxidants into a β-CD based matrix, while the controlled release of antioxidants in model formulations is mainly due to hydrophobic interactions. Results obtained in this study can be further used for studying the particular antioxidants (namely rutin or silibinin, quantified, for example, by liquid chromatographic techniques) for their transdermal transport and biological effects in innovatively designed pharmaceutical formulations that can be obtained using "green" methods and materials.