Novel Omeprazole Delayed Release Orally Disintegrating Tablets for Enhanced Patient Compliance: A Case of Model Informed Formulation Development

Abstract

The advanced in silico simulation tools, such as physiologically based biopharmaceutics models (PBBM) or physiologically based pharmacokinetic models (PBPK), play critical role in model informed formulation development. This approach has been successfully implemented in the present case for development of novel omeprazole delayed-release orally disintegrating tablets (ODT) formulation, aimed to enhance patient compliance. PBBM was developed using physicochemical, biopharmaceutical, and dissolution data. The dissolution studies for pilot formulations were conducted in bio predictive media in fasting (0.1N HCl followed by pH 6.8) and fed (pH 5 followed by pH 6.8) conditions. The model was extensively validated in three stages: pilot fasted, pilot fed virtual bioequivalence and food effect assessments. Impressively, the model was able to predict both passed and failed batches appropriately. Based on insights from the pilot study, a higher scale pivotal formulation was optimized. Prospective predictions were made for pivotal formulations using validated model and bio results were found to be in line with model predictions in fasting condition. Overall, a rationale and patient compliant formulation was developed using innovative modeling approach and filed to regulatory agency. The novel omeprazole formulation enhanced patient compliance through ease of administration thereby circumventing challenges of conventional formulation.