Predicting Food Effects on Oral Extended-Release Drug Products: A Retrospective Evaluation

Area of Science:

• Pharmacokinetics
• Drug Delivery Systems
• Gastrointestinal Physiology

Background:

• Extended-release (ER) drug products may exhibit different food effects compared to immediate-release (IR) formulations.
• Postprandial physiological changes, such as delayed gastric emptying and prolonged intestinal transit, can influence oral drug absorption.
• Understanding region-specific intestinal absorption is crucial for predicting food effects on ER drugs.

Purpose of the Study:

• To investigate the impact of food on the pharmacokinetics of oral extended-release (ER) drug products.
• To evaluate the relationship between intestinal region-dependent absorption and food effects.
• To identify predictors for minimal food effects on ER drug exposure.

Main Methods:

• Analysis of 136 oral ER drug products approved by the US FDA (1998-2021).
• Review of drug release profiles under fasted and fed conditions.
• Assessment of fasted bioavailability (BA) relative to immediate-release (IR) products.
• Consideration of in vitro permeability data for high-solubility drugs.

Main Results:

• Out of 136 ER products, 31 showed increased AUC, 6 showed decreased AUC, and 99 showed unchanged AUC under fed conditions.
• ER products with a fasted relative BA of 80-125% compared to IR products generally show no substantial food effect on AUC.
• High in vitro permeability can predict no significant food effect on AUC for high-solubility ER drugs when fasted relative BA data is unavailable.

Conclusions:

• Food effects on ER products are often minimal and can be predicted by factors like fasted relative bioavailability and in vitro permeability.
• Intestinal region-dependent absorption plays a key role in determining food effects for ER formulations.
• The majority of ER products exhibit unchanged AUC under fed conditions, suggesting robust formulation design.