Pharm Res (2011) 28:1065–1073 DOI 10.1007/s11095-010-0357-6 RESEARCH PAPER Magnetic Resonance Imaging and Image Analysis for Assessment of HPMC Matrix Tablets Structural Evolution in USP Apparatus 4 Piotr Kulinowski & Przemysław Dorożyński & Anna Młynarczyk & Władysław P. Węglarz Received: 27 September 2010 / Accepted: 15 December 2010 / Published online: 23 December 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com ABSTRACT Purpose The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. Methods A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow- through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmen- tation algorithms due to trimodal structure of the image intensity histograms. Results Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. Conclusions The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 P. Kulinowski (*) : A. Młynarczyk : W. P. Węglarz Department of Magnetic Resonance Imaging Institute of Nuclear Physics Polish Academy of Sciences ul. Radzikowskiego 152 31-342 Kraków, Poland e-mail: Piotr.Kulinowski@ifj.edu.pl P. Dorożyński Department of Pharmaceutical Technology and Biopharmaceutics Pharmaceutical Faculty, Jagiellonian University ul. Medyczna 9 30-688 Kraków, Poland was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/ FTIR studies. KEY WORDS flow-through cell . HPMC . image analysis . magnetic resonance imaging . USP Apparatus 4 ABBREVIATIONS CR controlled release FOV field of view FTIR Fourier transform infrared FTIR-ATR Fourier transform infrared-attenuated total reflection HPMC Hydroxypropylmethylcellulose MR magnetic resonance MRI magnetic resonance imaging TE echo time TR repetition time USP United States Pharmacopoeia VIS macro-photography INTRODUCTION Hydrophilic polymer matrix systems are widely used for controlled release (CR) formulations (1). The distribution and mobility of water within the polymeric systems and their influence on properties of particular regions of the matrix during hydration are key factors for the identification of drug dissolution and transport mechanisms. A number of theoretical studies that attempt to develop models of these mechanisms are present in the literature and were recently reviewed by Grassi et al. (2) and Sieppman et al. (3). Most of the studies concerned in vitro drug release prediction. This approach seems to be unsatisfactory because the literature