| Summary: | Important current developments in pharmaceutical science are in the area of formulation
technology where the ultimate goal is to control the rate and duration of drug release.
Swelling-controlled drug delivery systems utilize the swelling of a hydrophilic polymer to
control drug release. NMR spectroscopy and NMR imaging are presented as non-invasive
and non-destructive techniques that can provide both chemical and spatial information
during the swelling of such controlled release systems.
The tablet system chosen for this study contained hydroxypropylmethylcellulose
(HPMC) as the hydrophilic polymer and one of two fluorinated compounds, triflupromazine-
HCl or 5-fluorouracil, as model drugs. The geometry for the tablet swelling was chosen
to simplify the system to one where the transport processes were one-dimensional. Water
distributions were determined by one-dimensional ¹H NMR imaging. HPMC distributions
were not measured directly but were calculated from the calibration of the T₂ relaxation
times of the water as a function of HPMC concentration. The presence of air bubbles
in the swollen tablet resulted in experimentally determined polymer distributions which
contained up to 45% more HPMC than the known weight of HPMC in the tablet. When
the air in the tablet was removed under vacuum prior to the imaging experiment, the total
weight of HPMC from the experimental distributions was much closer to the actual weight
of HPMC in the tablet.
The comparison of the polymer distribution and the drug distributions, obtained
from one-dimensional ¹⁹F NMR imaging investigations of tablets containing model drugs,
showed that most of the triflupromazine-HCl remained within the swollen polymer tablet
while more of the 5-fluorouracil was able to escape. The critical condition for drug release from the tablet was the relationship between the diffusivity of the drug and the expansion
rate of the tablet. For triflupromazine-HCl, the required rate of diffusion was not reached
until the region of tablet erosion. In contrast, the diffusion coefficient of 5-fluorouracil in
30% HPMC was large enough that the drug diffused faster than the polymer expanded.
Preliminary modelling calculations assuming Fickian diffusion and a segmented-tablet
model were performed. === Science, Faculty of === Chemistry, Department of === Graduate
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