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 1H and 19F 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 approximately 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.
Fyfe
C A
CA
Department of Chemistry, University of British Columbia, 2036 Main Mall, BC, V6T, Vancouver, Canada.
Blazek-Welsh
A I
AI
D002138:Calibration; D005472:Fluorouracil / Q000008:administration & dosage; D065347:Hypromellose Derivatives; D008279:Magnetic Resonance Imaging; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D013997:Time Factors; D014273:Triflupromazine / Q000008:administration & dosage
D004364:Pharmaceutical Preparations; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D014273:Triflupromazine; D005472:Fluorouracil