1. Pharmacokinetic modeling and simulations of gastrointestinal transit effects on drug pharmacokinetics from enteric-coated pellet formulations and their applications. 2. Development of crushable enteric-coated formulations. 3. Development of leaky enteric-coated pellets formulations.
Effects of gastrointestinal transit on plasma concentrations of drugs from enteric-coated pellet formulations were demonstrated using pharmacokinetic models describing plasma concentrations of drugs from various enteric-coated pellet formulations. Gastric emptying time, lag time of emptying, and drug release rate from pellets in the small intestine, along with other pharmacokinetic parameters of drugs, were used to construct pharmacokinetic models. The models were then evaluated by comparing simulated plasma concentrations of model drugs from Monte Carlo simulations to observed plasma concentrations of these drugs from the literature. Results showed that the models described plasma concentrations of drugs from enteric-coated pellet formulations very well. Pharmacokinetic models describing plasma concentrations of drug from mixed immediate-release and enteric-coated pellet formulations were also used in simulations of bioequivalence studies. Results from the research are very useful in designing generic products of mixed pellet formulation and in refining or selecting the final product for actual bioequivalence study.