Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ - is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

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DOIResolve DOI: http://doi.org/10.1007/s11095-014-1334-2
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TypeArticle
Journal titlePharmaceutical Research
ISSN0724-8741
Volume31
Issue9
Pages23832392; # of pages: 10
AbstractPurpose: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. Methods: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. Results: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. Conclusions: We have introduced a new paradigm in the characterization of hydrating matrices using 1H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods. © 2014 The Author(s).
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biodiagnostics (IBD-IBD)
Peer reviewedYes
NRC number56024
NPARC number21272186
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Record identifier6e68134c-0c23-48e9-9ed4-0e36211b3765
Record created2014-07-23
Record modified2016-05-09
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