The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix...

Area of Science:

• Pharmaceutical Sciences
• Biomedical Engineering
• Materials Science

Background:

• Imaging techniques like MRI are supplementary to dissolution tests.
• The direct relationship between dissolution and imaging data has been largely overlooked.
• Controlled-release drug products require precise understanding of drug release mechanisms.

Purpose of the Study:

• To assess the feasibility of correlating MRI and dissolution data.
• To elucidate dissolution profile features such as kinetics, kinetics changes, and variability.
• To establish a causal link between matrix morphology changes and drug dissolution.

Main Methods:

• Utilized magnetic resonance imaging (MRI) within a USP4 dissolution apparatus.
• Employed machine learning for image segmentation of controlled-release matrix tablets.
• Conducted dissolution testing with piecewise dissolution modeling.
• Analyzed combined MRI and dissolution data using statistical methods, including multiple linear regression.

Main Results:

• Zeroth-order release was linked to internal structure evolution and core disappearance.
• Internal structure changes, specifically the interplay between regions, influenced release kinetics.
• Core disappearance led to shifts in dissolution kinetics from zeroth order to nonlinear.
• Drug dissolution variability increased with the progression of core disappearance.

Conclusions:

• It is feasible to parameterize micro/meso morphological changes in hydrated, swellable matrices using MRI.
• A causal relationship between morphological changes and drug dissolution can be established.
• Combined MRI and dissolution testing offers new perspectives for controlled-release drug product development.