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Zero-Order Drug Release from Hydrocolloid Matrices

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Abstract

Matrices are manufactured by direct compression of a powder mixture of a polymer, e.g., methylhydroxypropyl cellulose (MHPC) or polyvinylalcohol (PVAI), and a drug. The following factors that can influence the drug release mode were investigated at constant surface: (i) polymer solution viscosity, glass transition temperature, and swelling; (ii) drug concentration in the matrix and solubility; and (iii) conditions of release experiment (hydrodynamics). In the case of zero-order release profiles (hydrocolloids with low viscosities), only the dissolution of the polymer appears to control the drug release rate. Factors accelerating polymer dissolution resulted in higher release rates. Comparison of swollen and dry hydrocolloid matrices shows that the duration and kinetics of drug release were not controlled by the swelling front moving into the dry polymer, and water penetration and relaxation were not rate controlling. Therefore, the glass transition temperature had no effect on drug release from these hydrocolloids. The higher the hydrodynamic stress exerted on the eroding hydrocolloid, the faster the resulting drug release as a result of accelerated polymer dissolution. With hydrocolloids of very high viscosity the polymer dissolution is slow, and drug relese from the swollen gel appears to be controlled by diffusion according to kinetics of the Higuchi type.

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REFERENCES

  1. T. Higuchi. Mechanism of sustained-action medication. J. Pharm. Sci. 52:1145–1149 (1963).

    Google Scholar 

  2. S. K. Baveja and K. Padmalatha Devi. Sustained release tablet formulation of metoprolol tartrate. Indian J. Pharm. Sci. 47:78 (1985).

    Google Scholar 

  3. S. K. Baveja, K. V. Ranga Rao, and K. Padmalatha Devi. Zero-order release hydrophilic matrix tablets of β-adrenergic blockers. Int. J. Pharm. 39:39–45 (1987).

    Google Scholar 

  4. P. Catellani, G. Vaona, P. Plazzi, and P. Colombo. Compressed matrices: Formulation and drug release kinetics. Acta Pharm. Technol. 34:38–41 (1988).

    Google Scholar 

  5. P. Colombo, A. Gazzaniga, C. Caramelle, U. Conte, and A. La Manna. In vitro programmable zero-order release drug delivery system. Acta Pharm. Technol. 33:15–20 (1987).

    Google Scholar 

  6. H. E. Huber, L. B. Dale, and G. L. Christenson. Utilization of hydrophilic gums for the control of drug release from tablet formulations. I. Disintegration and dissolution behavior. J. Pharm. Sci. 55:974–976 (1966).

    Google Scholar 

  7. B. Huet de Barochez, J. S. Julien, F. Lapeyre, S. Horvath, and A. Cuiné. Influence of drug solubility in the formulation of hydrophilic matrices. Drug Dev. Ind. Pharm. 15:2197–2212 (1989).

    Google Scholar 

  8. R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, and N. A. Peppas. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm. 15:25–35 (1983).

    Google Scholar 

  9. K. V. Ranga Rao, K. Padmalatha Devi, and P. Buri. Influence of molecular size and water solubility of the solute on its release from swelling and erosion controlled polymeric matrices. J. Control. Release 12:133–141 (1990).

    Google Scholar 

  10. J. J. Shah, S. M. Bolton, and A. W. Malick. Hydroxypropylcellulose. Evaluation of effects of various factors on sustained-release characteristics of salicylic acid from compressed tablets. J. Pharm. Sci. 76:S297 (1987).

    Google Scholar 

  11. A. Wermerskirchen. Haftvermögen und Freigabeverhalten von selbsthaftenden Bukkalfilmen in vitro und in vivo, Dissertation, Bonn, 1989.

  12. N. L. Thomas, and A. H. Windle. Case-II-swelling of PMMA sheet in methanol. J. Membr. Sci. 3:337–342 (1978).

    Google Scholar 

  13. A. Urtti, M. Juslin, and O. Miinalainen. Pilocarpine release from hydroxypropyl-cellulose-polyvinylpyrrolidone matrices. Int. J. Pharm. 25:165–178 (1985).

    Google Scholar 

  14. H. B. Hopfenberg, and H. L. Frisch. Transport of organic micromolecules in amorphous polymers. J. Polym. Sci. B7:405–409 (1969).

    Google Scholar 

  15. H. Lapidus and N. G. Lordi. Some factors affecting the release of a water-soluble drug from a compressed hydrophilic matrix. J. Pharm. Sci. 55:840–843 (1966).

    Google Scholar 

  16. R. Anders and H. P. Merkle. Evaluation of laminated mucoadhesive patches for buccal drug delivery. Int. J. Pharm. 49:231–240 (1989).

    Google Scholar 

  17. G. Vankatesh, W. M. Eichkoff, and K. Vishnupad. Studies on mechanism of drug release from monolithic delivery devices. J. Pharm. Sci. 76:S305 (1987).

    Google Scholar 

  18. P. Y. Wang. Controlled release by a combination chemical matrix. Proc. Int. Symp. Control. Release Bioact. Mater. 13:39–40 (1986).

    Google Scholar 

  19. P. I. Lee. Diffusional release of a solute from a polymeric matrix—Approximate analytical solution. J. Membr. Sci. 7:255–275 (1980).

    Google Scholar 

  20. P. I. Lee and N. A. Peppas. Prediction of polymer dissolution in swellable controlled-release systems. J. Control. Release 6:207–215 (1987).

    Google Scholar 

  21. R. S. Harland, A. Gazzaniga, M. E. Sangalli, P. Colombo, and N. A. Peppas. Drug/polymer matrix swelling and dissolution. Pharm. Res. 5:488–494 (1988).

    Google Scholar 

  22. J. Möckel. Mechanismus kontinuierlicher und gepulster Arzneistofffreisetzung aus Hydrokolloideinbettungen, Dissertation, Düsseldorf, 1990.

  23. D. Voegele. Modellierung von Auflöseprofilen mit Hilfe der allgemeinen Exponentialfunktion auf Basis der Momente der Auflösezeiten. Abstract, Vortrags-und Diskussionsveranstaltung des Instituts für Pharmazeutische Technologie der Heinrich-Heine-Universität Düsseldorf, Leinsweiler, 1988.

  24. D. Voegele, D. Brockmeier, and H. M. von Hattinberg. The mean-transit-time as an aid in the development of galenical dosage forms. In N. Rietbrock, B. G. Woodcock, and G. Neuhaus (eds.), Methods in Clinical Pharmacology, Vieweg, Braunschweig, 1980, pp. 94–99.

    Google Scholar 

  25. A. Heyd, D. O. Kildsig, and G. S. Banker. Dissolution of macromolecules. J. Pharm. Sci. 58:586–588 (1969), 59:947–949 (1970).

    Google Scholar 

  26. K. Ueberreiter. The solution process. In J. Crank and G. S. Park (eds.), Diffusion in Polymers, Academic Press, London, 1967, pp. 219–257.

    Google Scholar 

  27. K. Ueberreiter and F. Asmussen. Velocity of dissolution of polymers. J. Polym. Sci. 57:187–208 (1962).

    Google Scholar 

  28. Hoechst AG, Mowiol Polyvinyalkohol, Company Information, 1984.

  29. H. P. Merkle, Untersuchungen an Einbettungen von Arzneistoffen in Polyvinylpyrrolidon, Habilitationsarbeit, Heidelberg, 1979.

  30. H. Nogami, T. Nagai, and A. Kondo. Dissolution kinetics of polyvinylpyrrolidone of various molecular weights. Chem. Pharm. Bull. 18:2290–2296 (1970).

    Google Scholar 

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Authors and Affiliations

  1. Galenical Development, Boehringer Mannheim GmbH, D-68, Mannheim, 31, Germany

    Jörn E. Möckel

  2. Institute for Pharmaceutical Technology, Heinrich-Heine-University, Universitätsstr. 1, D-4000, Düsseldorf, 1, Germany

    Bernhard C. Lippold

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  1. Jörn E. Möckel
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  2. Bernhard C. Lippold
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Möckel, J.E., Lippold, B.C. Zero-Order Drug Release from Hydrocolloid Matrices. Pharm Res 10, 1066–1070 (1993). https://doi.org/10.1023/A:1018931210396

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