Quantitative NMR imaging study of the mechanism of drug release from swelling hydroxypropylmethylcellulose tablets

NMR imaging has been used to study the release behavior of two model drugs, triflupromazine-HCl and 5-fluorouracil, from swelling hydroxypropylmethylcellulose (HPMC) tablets. Preliminary experiments were performed on equilibrium mixtures of drug, polymer and water to determine how properties such as NMR relaxation parameters and self-diffusion were affected by the drug and polymer concentrations. The tablet swelling was restricted to one dimension and distributions of the water and model drugs were obtained by H-1 and F-19 imaging, respectively. The HPMC distribution at each time in the swelling process was determined indirectly from its effect on the relaxation parameters of the water and the drugs. In the one-dimensional swelling tablet, distributions of drug and polymer were compared to determine what factors influenced the release of drug from the swelling tablet. The distributions for triflupromazine-HCl and HPMC paralleled each other and the drug was only released at the eroding edge of the tablet where the HPMC concentration dropped below 10%. In contrast, 5-fluorouracil was released much more rapidly from the tablet and appeared to escape by diffusion from regions as high as 30% HPMC. An empirical measure of the rate of tablet edge movement can be obtained from plots of the edge position as a function of the square root of time. For HPMC, the rate of tablet expansion was determined in this way to be (2.4+/-0.8)x10(-6) cm(2) s(-1). The self-diffusion of triflupromazine-HCl in equilibrated mixtures of similar composition to the eroding tablet edge is similar to 3x10(-6) cm(2) s(-1) while the self-diffusion coefficient of 5-fluorouracil remained higher than this value until the HPMC concentration reached about 30%. This comparison of ’diffusion’ properties may be useful in predicting the mechanism of drug release from other swelling hydrophilic matrix systems. (C) 2000 Elsevier Science B.V. All rights reserved.