Abstract.
Magnetic resonance imaging is used to map the ingress of water into a nominally nonswelling polymer-matrix slow-release drug delivery device comprising a compact of particulate Eudragit polymer and Diltiazem Hydrochloride drug. It is shown that the water ingresses with the square root of time: that is, it is "Fickian-like"; and that the release depends only weakly on the particulate size. A dissolution–diffusion model specifically incorporating the drug particulate size is developed to describe the release mechanism. The experimental results are in accord with the model. It is further shown theoretically that the release should become "non-Fickian-like" and particle size dependent if the drug dissolution constant were to be reduced substantially, an observation explained using a dimensionless scaling argument that compares the dissolution and diffusion rates. It has, however, not been possible to perform experiments in this different regime with the same materials.
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Singh, S.K., Fan, L.T.: Biotechnol. Prog. 2, 145–156 (1986)
Brazel, C.S., Peppas, N.A.: Eur. J. Pharm. Biopharm. 49, 47–58 (2000)
Kazarian, S.G., Chan, K.L.A.: Macromolecules 36, 9866–9872 (2003)
Vergote, G.J., Vervaet, C., Remon, J.P., Haemers, T., Verpoort, F.: Eur. J. Pharm. Sci. 16, 63–67 (2002)
Bowtell, R., Sharp, J.C., Peters, A., Mansfield, P., Rajabi-Siahboomi, A.R., Davies, M.C., Melia, C.D.: Magn. Reson. Imaging 12, 361–364 (1994)
Fahie, B.J., Nangia, A., Chora, S.K., Fyfe, C.A., Grondey, H., Blazek, A.: J. Controlled Release 51, 179–184 (1998)
Fyfe, C.A., Blazek-Welsh, A.I.: J. Controlled Release 68, 313–333 (2000)
Richardson, J.C., Bowtell, R.W., Mäder, K., Melia, C.D.: Adv. Drug Delivery Rev. 57, 1191–1209 (2005)
Narasimhan, B.: Adv. Drug Delivery Rev. 48, 195–210 (2001)
Kanjickal, D.G., Lopina, S.T.: Crit. Rev. Ther. Drug Carrier Syst. 21, 345–386 (2004)
Frenning, G., Stromme, M.: Int. J. Pharm. 250, 137–145 (2003)
Schreiner, T.S., Schaefer, U.F., Loth, H.: J. Pharm. Sci. 94, 120–133 (2005)
Peppas, A.N.: J. Biomed. Mater. Res. 17, 1079–1087 (1983)
Harland, R.S., Dubernet, C., Benoit, J.-P., Peppas, N.A.: J. Controlled Release 7, 207–215 (1988)
Azarmi, S., Farid, J., Nokhodchi, A., Bahari-Saravi, S.M., Valizadeh, H.: Int. J. Pharm. 246, 171–177 (2002)
Omari, D.M., Sallam, A., Abd-Elbary, A., El-Samaligy, M.: Int. J. Pharm. 274, 85–96 (2004)
Oth, M.P., Moes, A.J.: Int. J. Pharm. 55, 157–164 (1989)
Callaghan, P.T.: Principles of Nuclear Magnetic Resonance Microscopy, pp. 133–138. Clarendon Press, Oxford (1993)
Crank, J.: The Mathematics of Diffusion, 2nd edn., p. 105. Clarendon Press, Oxford (1975)
Bird, R.B., Steward, W.E., Lightfoot, E.N.: Transport Phenomena, 2nd edn. Wiley, New York (2002)
Wallin, M., Glover, P.M., Hellgren, A.C., Keddie, J.L., McDonald, P.J.: Macromolecules 33, 8443–8452 (2000)
Noyes, A.A., Whitney, W.R.: J. Am. Chem. Soc. 19, 930–934 (1897)
Thomas, N.L., Windle, A.H.: Polymer 23, 529–542 (1982)
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Authors' address: Peter J. McDonald, Department of Physics, School of Electronics and Physical Sciences, University of Surrey, Guildford, GU2 7XH, UK
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Karakosta, E., McDonald, P. An MRI Analysis of the Dissolution of a Soluble Drug Incorporated within an Insoluble Polymer Tablet. Appl Magn Reson 32, 75–91 (2007). https://doi.org/10.1007/s00723-007-0001-8
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DOI: https://doi.org/10.1007/s00723-007-0001-8