NMR imaging investigations of swelling-controlled drug delivery

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 ofChemistry, Department ofGraduat