CAREER: Mechanistic Studies and Modeling of Self-Emulsifying Drug Delivery
The research objectives of the project are: (1) to develop insight into the physical phenomena and physicochemical parameters governing emulsion function in the gastrointestinal (GI) environment, and (2) develop a computational model to predict the influence of emulsions on oral compound absorption. There are many studies in the literature reporting enhancement in drug solubility and/or oral bioavailability by specific emulsion formulations. The proposed approach is to break down the overall function of emulsions in the GI tract into comprising processes and study these processes using a comprehensive set of emulsion formulations statistically designed to test the possible range of physical and chemical properties (oil structure, surfactant hydrophilic-lipophilic balance, drug logP, etc.). Key mechanistic processes of emulsion function in the GI environment will be simulated in vitro. Specifically, the ability to form an emulsion in the mixed GI environment and kinetics of drug release, emulsion digestion, and intestinal permeability enhancement will be measured and related to formulation physicochemical properties. Appropriate kinetic expressions and dependence of kinetic parameters on formulation properties will then be integrated into a systems-based model. The ability of the model to predict the influence of emulsions on drug absorption will be validated using in vitro and in vivo experiments. The ability to predict when and how emulsions influence oral compound absorption will have a significant impact on societal health. Rational emulsion design will realize the potential of this technology to orally deliver drugs that may otherwise not be viable products, and insight will be gained into the ‘food effect’, a poorly understood phenomenon that influences the oral bioavailability of most drugs.
Northeastern University’s College of Engineering is home to numerous federally-funded research centers and an array of leading-edge projects and initiatives that advance discovery and new knowledge in health, sustainability, and security.