Drug Dissolution in Oral Drug Absorption: Workshop Report

Abstract

The in-person workshop “Drug Dissolution in Oral Drug Absorption” was held on May 23–24, 2023, in Baltimore, MD, USA. The workshop was organized into lectures and breakout sessions. Three common topics that were re-visited by various lecturers were amorphous solid dispersions (ASDs), dissolution/permeation interplay, and in vitro methods to predict in vivo biopharmaceutics performance and risk. Topics that repeatedly surfaced across breakout sessions were the following: (1) meaning and assessment of “dissolved drug,” particularly of poorly water soluble drug in colloidal environments (e.g., fed conditions, ASDs); (2) potential limitations of a test that employs sink conditions for a poorly water soluble drug; (3) non-compendial methods (e.g., two-stage or multi-stage method, dissolution/permeation methods); (4) non-compendial conditions (e.g., apex vessels, non-sink conditions); and (5) potential benefit of having both a quality control method for batch release and a biopredictive/biorelevant method for biowaiver or bridging scenarios. An identified obstacle to non-compendial methods is the uncertainty of global regulatory acceptance of such methods.

Introduction

The in-person workshop “Drug Dissolution in Oral Drug Absorption” was held on May 23–24, 2023, in Baltimore, MD, USA, and was organized by the University of Maryland Center for Excellence in Regulatory Science and Innovation (M-CERSI). The workshop was organized into lectures and breakout sessions. The purpose of the workshop was to facilitate dialog between academic, industrial, and regulatory drug development scientists about current phenomena and methods in oral drug product dissolution method development and application. The lecture notes from this workshop are posted at: https://cersi.umd.edu/drug-dissolution-oral-drug-absorption-workshop. The workshop agenda is included in Supplementary materials.

Topics included in vivo dissolution and drug absorption; in vivo gastrointestinal tract (GIT) imaging and dynamics; regulatory considerations for dissolution method development, including non-compendial methods; and critical amorphous solid dispersion (ASD) properties and dissolution method development. Over 100 attendees participated.

The objective of this workshop report is to summarize the lectures and breakout session discussions. The workshop included 13 lectures on advances in drug dissolution. In this workshop report, lectures are briefly described in three sub-sections: Lectures involving supersaturation; lectures involving dissolution/permeation systems; and lectures involving oral biopharmaceutics prediction and understanding. This sectioning of lecture content reflects the three common topics that were re-visited by various lecturers and via several breakout discussions.

The workshop included 10 breakout sessions to provide opportunities to discuss in small groups the current challenges and limitations, including emerging approaches and techniques for complex oral formulations. Table I lists breakout session topics and main questions addressed. Common themes across breakout sessions were the following: (1) meaning and assessment of “dissolved drug,” (2) issues of requiring sink conditions for a poorly water soluble drug; (3) non-compendial methods, (4) non-compendial conditions; and (5) potential benefit of a biopredictive/biorelevant method that supplements a quality control (QC) method. An identified obstacle to non-compendial methods is the uncertainty of global regulatory acceptance of such methods.

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Raines, K., Agarwal, P., Augustijns, P. et al. Drug Dissolution in Oral Drug Absorption: Workshop Report. AAPS J 25, 103 (2023). https://doi.org/10.1208/s12248-023-00865-8

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