The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.
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.
Institute of Technology, The Pedagogical University of Cracow, ul. Podchorążych 2, 30-084, Kraków, Poland. pkulino@up.krakow.pl.
Piotr
P
Kulinowski
Institute of Technology, The Pedagogical University of Cracow, ul. Podchorążych 2, 30-084, Kraków, Poland.
Wiktor
W
Hudy
Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688, Kraków, Poland.
Aleksander
A
Mendyk
Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688, Kraków, Poland.
Ewelina
E
Juszczyk
Department of Magnetic Resonance Imaging, Institute of Nuclear Physics PAN, ul. Radzikowskiego 152, 31-342, Kraków, Poland.
Władysław P
WP
Węglarz
Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688, Kraków, Poland.
Renata
R
Jachowicz
Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688, Kraków, Poland.
Przemysław
P
Dorożyński
D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D000069348:Quetiapine Fumarate / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D000069348:Quetiapine Fumarate; D065347:Hypromellose Derivatives
dissolution test; image analysis; machine learning; magnetic resonance imaging (MRI); quetiapine fumarate