Abstract
The transient dynamic swelling and dissolution behavior during drug release from hydroxypropylmethyl cellulose (HPMC) matrices was investigated using fluorescein as a model drug. A new flow-through cell capable of providing a well-defined hydrodynamic condition and a non-destructive mode of operation was designed for this purpose to assess the associated moving front kinetics. The results obtained show a continuous increase in transient gel layer thickness irrespective of the polymer viscosity grade or drug loading. This is attributed to the faster rate of swelling solvent penetration than that of polymer dissolution under the present experimental condition. On the other hand, the observed shrinkage of sample diameter over a longer time period demonstrates that polymer dissolution does indeed occur in HPMC matrices. Further, both the rates of polymer swelling and dissolution as well as the corresponding rate of drug release increase with either higher levels of drug loading or lower viscosity grades of HPMC. For water-soluble drugs, the present results suggest that the effect of HPMC dissolution on drug release is insignificant and the release kinetics are mostly regulated by a swelling-controlled diffusional process, particularly for higher viscosity grades of HPMC.
Similar content being viewed by others
REFERENCES
G. L. Christenson and L. B. Dale. Sustained release tablet. U.S. Patent, 3,065,143, 1962.
D. A. Alderman. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int. J. Pharm. Tech. & Prod. Mfr. 5:1–9 (1984).
P. I. Lee and N. A. Peppas. Prediction of polymer dissolution in swellable controlled-release systems. J. Controlled Rel. 6:207–215 (1987).
P. I. Lee. Diffusional release of a solute from a polymeric matrix-approximate analytical solutions. J. Membrane Sci. 7:255–275 (1980).
P. I. Lee. Diffusion-controlled matrix systems. In A. Kydonieus (ed.), Treatise on Controlled Drug Delivery, Marcel Dekker, New York, 1992, pp. 155–197.
P. Colombo, A. Gazzaniga, C. Caramella, U. Conte, and A. La Manna. In vitro programmable zero-order release drug delivery system. Acta Pharm. Technol. 33:15–20 (1987).
U. Conte, P. Colombo, A. Gazzaniga, M. E. Sangalli, and A. La Manna. Swelling-activated drug delivery systems. Biomaterials. 9:489–493 (1988).
E. E. Parsonage, N. A. Peppas, and P. I. Lee. Properties of positive resists. II. Dissolution characteristics of irradiated poly(methyl methacrylate-co-maleic anhydride). J. Vacuum Sci. Technol., Pt. B. 5:538–545 (1987).
P. Sakelariou, R. C. Rowe, and E. F. T. White. The thermomechanical properties and glass transition temperatures of some cellulose derivatives used in film coating. Int. J. Pharm. 27:267–277 (1985).
E. Doelker. Swelling behavior of water-soluble cellulose derivatives. In Brannon-Peppas L, Harland RS (eds.), Absorbent Polymer Technology, Elsevier, New York, 1990, pp. 125–145.
J. L. Ford, M. H. Rubinstein, F. McCaul, J. E. Hogan, and P. J. Edgar. Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropylmethylcellulose matrix tablets. Int. J. Pharm. 40:223–234 (1987).
R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, and N. A. Peppas. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm. 15:23–35 (1983).
R. B. Bird, W. E. Stewart, and E. N. Lightfoot. Transport Phenomena. John Wiley & Sons, New York, 1960, Chapter 21.
P. I. Lee. Dimensional changes during drug release from a glassy hydrogel matrix. Polym. Commun. 24:45–47 (1983).
P. I. Lee and C.-J. Kim. Probing the mechanisms of drug release from hydrogels. J. Control. Rel. 16:229–236 (1991).
K. Ueberreiter. The solution process. In J. Crank and G. S. Park (eds.), Diffusion in Polymers, Academic Press, New York, 1968, pp. 219–257.
P. I. Lee. Interpretation of drug-release kinetics from hydrogel matrices in terms of time-dependent diffusion coefficients. In P. I. Lee and W. R. Good (eds.), Controlled Release Technology: Pharmaceutical Applications, ACS Sym. Ser. No. 348, American Chemical Society, Washington, D.C., 1987, pp. 71–83.
P. I. Lee and S. K. Lum. Swelling-induced zero-order release from rubbery polydimethylsiloxane beads. J. Control. Rel. 18:19–24 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pham, A.T., Lee, P.I. Probing the Mechanisms of Drug Release from Hydroxypropylmethyl Cellulose Matrices. Pharm Res 11, 1379–1384 (1994). https://doi.org/10.1023/A:1018975318805
Issue Date:
DOI: https://doi.org/10.1023/A:1018975318805