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Quantitative magnetic resonance methods in pharmaceutical research
1  Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK

Abstract: The use of magnetic resonance imaging (MRI) as a tool in pharmaceutical research dates back to the early 1990s where traditional spin-echo magnetic resonance imaging was to investigate the swelling of hydrating hydroxypropylmethylcellulose (HPMC) tablets. Since then there has been a vast amount of work published in the literature concerning the use of magnetic resonance imaging and its application to pharmaceutical systems. However, many of these previous studies were not fully quantitative and generally only gave qualitative information. The aim of this paper is to focus on the use of state-of-the art fast quantitative magnetic resonance techniques and how they are used to extract quantitative information that is of direct relevance to pharmaceutical research. The paper will focus on the application of fast multi-nuclear quantitative MRI techniques to study the dynamics of tablet dissolution, drug mobilisation and tablet erosion in a standard USP-4 dissolution cell operated under bio-relevant conditions. We show that it is possible to obtain two-dimensional spatially resolved maps within the tablet in less than two minutes. We demonstrate it is possible to obtain local information, within the tablet, regarding dissolution media concentration, dissolution media hydrodynamics and both Fickian and self-diffusion transport coefficients. In addition, we show it is also possible, through multi-nuclear MRI, to gain new insights into drug mobilisation within a tablet during the dissolution process.