Quantitative Ultra-Fast MRI of HPMC Swelling and Dissolution

被引:63
作者
Chen, Ya Ying [1 ]
Hughes, L. P. [2 ]
Gladden, L. F. [1 ]
Mantle, M. D. [1 ]
机构
[1] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 3RA, England
[2] AstraZeneca, Pharmaceut & Analyt R&D, Macclesfield SK10 2NA, Cheshire, England
基金
英国工程与自然科学研究理事会;
关键词
quantitative MRI; RARE; HPMC; swelling; dissolution; RELEASE DOSAGE FORMS; MATRIX TABLETS; DRUG-RELEASE; HYDROXYPROPYLMETHYLCELLULOSE HPMC; DIFFUSION MEASUREMENTS; FIELD GRADIENT; IMAGING METHOD; GEL LAYER; RESONANCE; WATER;
D O I
10.1002/jps.22110
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
For the first time quantitative Rapid Acquisition with Relaxation Enhancement (RARE) based ultra-fast two-dimensional magnetic resonance imaging has been used to follow the dissolution of hydroxypropylmethyl cellulose (HPMC) in water Quantitative maps of absolute water concentration, spin spin relaxation times and water self-diffusion coefficient are obtained at a spatial resolution of 469 mu m in less than 3 min each. These maps allow the dynamic development of the medium release rate HPMC/water system to be followed. It is demonstrated that the evolution of the gel layer and, in particular, the gradient in water concentration across it, is significantly different when comparing the quantitative RARE sequence with a standard (nonquantitative) implementation of RARE The total gel thickness in the axial direction grows faster than that in the radial direction and that the dry core initially expands anisotropically. Additionally, while HPMC absorbs a large amount of water during the dissolution process, the concentration gradient of water within the gel layer is relatively small. For the first time MRI evidence is presented for a transition swollen glassy layer which resides between the outer edge of the dry tablet core and the inner edge of the gel layer. (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3462-3472, 2010
引用
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页码:3462 / 3472
页数:11
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