(92g) Drug Release From Highly Concentrated Emulsions

In the field of controlled release technology for new drugs, models that can predict its delivery during application are important for device design. The main objective of this work is to develop a predictive model able to describe the drug delivery from highly concentrated water in oil emulsions. Concentrated emulsions present many interesting properties: high volume fraction of dispersed phase (up than 0.88) and gel-like texture. These systems consist of deformed droplets dispersed in a continuous film. Their structure's characteristics make them favourable for their use as releasing material. A combination of different transfer mechanisms has been implemented in a mathematical model in order to simulate release experiments under different operating conditions (volume fraction, oil/surfactant ratio). A sensitivity analysis has been performed to point out the most relevant parameters affecting the drug's release: distribution size of the emulsion droplets, drug's partition and transfer coefficients. A preliminary experimental study has been made out to determine most of the model's parameters independently, so that the number of the fitting ones will be reduced. Partition coefficient of the drug for different surfactant concentrations has been obtained through an experimental study using high performance liquid chromatography analysis and compared to predictive models described in the literature (contribution group method: UNIFAC). Depending on the transfer mechanism, the corresponding drug diffusion coefficient in the continuous phase has been estimated using classical models. An original and simple technique has been used to determine indirectly the mean droplet size of the concentrated emulsions, through measurements of continuous phase's thickness by analysis of incoherent polarized steady light transport through emulsion samples. Simulated curves of drug release have been compared to experimental ones for small molecules (caffeine and mandelic acid) in order to validate the values of the model parameters and transfer processes. A good agreement between simulated and experimental release knetics is obtained. The model described in this work, finally appears to be an interesting tool to understand and quantify the transport phenomenon of drugs within highly concentrated emulsions by considering their complex structure and composition.