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NMR imaging investigations of swelling HPMC tablets

University of British Columbia

The use of controlled release formulations in the pharmaceutical industry offers several advantages over rapid release formulations. An important feature of controlled release formulations is the ability to release a drug for an extended period of time at a controlled rate. One example is hydroxypropylmethylcellulose (HPMC) which is a hydrophilic polymer that has the unique property that when exposed to water, it undergoes a volume expansion or swells resulting in a polymer concentration gradient. A drug combined with HPMC into a tablet has a drug diffusion behaviour that is determined by this HPMC concentration gradient. To gain further insight in terms of providing concentration information, NMR imaging was employed in the present work to investigate the swelling of pure HPMC tablets. One-dimensional swelling experiments exposed only one side of a flat face HPMC tablet to water and therefore limited the swelling to only one direction. These swelling experiments were carried out at the physiological temperature of 37 °C and at various temperatures to determine if a correlation existed between temperature and the swelling rate. The results indicated a dependence of the swelling rate on temperature with an increase in temperature resulting in a greater swelling rate. To provide a more realistic understanding of these swelling systems, a three-dimensional swelling experiment was also carried out to monitor the polymer concentration gradients in three-dimensions. In contrast to the one-dimensional swelling, the three-dimensional swelling of a pure HPMC tablet involved the water penetration into both flat faces and sides. Results indicated that the rate of expansion favoured the vertical swelling direction over the radial direction as expected. In an effort to predict the swelling behaviour, a mathematical model was employed to simulate the one-dimensional swelling of a series of tablets of different thicknesses. Evaluation of the model was done by comparing the theoretical to the experimental results. The mathematical model was limited in its ability to predict the swelling in one-dimension. It assumed that the swelling was a homogeneous, single component system which did not reflect the one-dimensional experimental results that indicated a less homogeneous and a more heterogeneous swelling process.

Thesis/Dissertation

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2009-08-17

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http://hdl.handle.net/2429/12300

Chemistry

University of British Columbia

UBCV

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