Abstract
In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.
Highlights
An understanding of drug release phenomena is crucial for the interpretation of properties and behavior of dosage form in vitro and in vivo
The richness and diversity of dissolution equipment, as well as experimental conditions, provide a wide range of their applications at the development stage of a medicinal product, in quality control, post-approval changes, or as a surrogate for in vivo studies [1]. The power of these techniques stems from their great sensitivity to variations in dosage form properties, which are reflected in changes of dissolution profile
The analysis of the dissolution data with KinetDS software revealed a change in the kinetics of drug release at the fourth hour
Summary
An understanding of drug release phenomena is crucial for the interpretation of properties and behavior of dosage form in vitro and in vivo. The richness and diversity of dissolution equipment, as well as experimental conditions, provide a wide range of their applications at the development stage of a medicinal product, in quality control, post-approval changes, or as a surrogate for in vivo studies [1]. The power of these techniques stems from their great sensitivity to variations in dosage form properties, which are reflected in changes of dissolution profile. There is a need to combine dissolution methods with other techniques to improve their specificity and to further elucidate the mechanisms of drug dissolution. The application of combined methods that integrate drug dissolution and imaging techniques has increased noticeably [3,4,5,6,7,8,9,10,11,12]
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