In vitro Methodologies for Evaluating Food Effects on Intraluminal Drug Disposition: Possibilities and Gaps

Today, with the progress and improvement of formulation technologies, lowly soluble drugs can be formulated well and maintain their high oral bioavailabilities. However, it is much harder to overcome the negative and positive food effects in any formulation and medicine. If negative and positive food effects can be predicted in the early developmental stage, it is much easier to formulate the dosage forms and move into the clinical trials. However, there is a huge gap among the formulation development, the early stage preclinical research, the late stage preclinical research, and the first stage of clinical research in terms of developing the appropriate oral dosage forms to reduce the food effects. This delay of appropriate oral dosage form development will largely impact the timeline of drug development. The early stage preclinical developmental scientists mainly focus on toxicity, efficacy, and PK linearity, the late stage preclinical developmental scientists start thinking of maximizing its oral bioavailability and, hence, formulation design. Formulation scientists know how to make an oral dosage form, analytical scientists know how to analyze dissolution profiles and raise potential risk for food effects, PK scientists and Biopharm scientists know the risk of food effects from PK study. However, those findings are usually late stage and will impact on the drug development. In this session, the current trend of the formulation for low soluble drugs and mitigation plans or reduction of food effects will be presented and discussed with the case studies. Additionally, what would be the best practice to mitigate or reduce the food effect’s risk and what scientists should look into, how to make a smooth transition from preclinical to clinical, would be discussed.