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Effect of Water Mobility on Drug Hydrolysis Rates in Gelatin Gels

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Abstract

The stability of drugs incorporated in gelatin gels was studied, with a focus on the water mobility in the gels. Trichlormethiazide hydrolysis and kanamycin-catalyzed flomoxef hydrolysis in gelatin gels were chosen as models for apparent first-order and second-order hydrolysis, respectively. The mobility of water in gelatin gels was determined by NMR, ESR, and dielectric relaxation spectroscopies. The amount of bound water in the gels was determined from dielectric relaxation spectra. Spin-lattice relaxation time of water determined by 17O NMR and rotational correlation time of an ESR probe determined by an ESR probing method were useful in determining the micro viscosity of the gels. The hydrolysis rate of trichlormethi-azide in the gels was found to depend on the amount of free water available for the reaction, while that of flomoxef depended on the micro viscosity of the gels, which reflected the mobility of water molecules. Thus the dependence of hydrolysis rates on the water mobility was influenced by the hydrolysis mechanism.

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REFERENCES

  1. P. I. Lee. Kinetics of drug release from hydrogel matrices. J. Control. Release 2:277–288 (1985).

    Google Scholar 

  2. J. Rosenblatt, W. Rhee, and D. Wallace. The effect of collagen fiber size distribution on the release rate of proteins from collagen matrices by diffusion. J. Control. Release 9:195–203 (1989).

    Google Scholar 

  3. Y. H. Bae, T. Okano, and S. W. Kim. Insulin permeation through thermo-sensitive hydrogels. J. Control. Release 9:271–279 (1989).

    Google Scholar 

  4. A. Domb, G. W. R. Davidson III, and L. M. Sanders. Diffusion of peptides through hydrogel membranes. J. Control. Release 14:133–144 (1990).

    Google Scholar 

  5. C. M. Klech, and J. H. Pari. Temperature dependence of non-Fickian water transport and swelling in glassy gelatin matrices. Pharm. Res. 6:564–570 (1989).

    Google Scholar 

  6. S. C. Chi and H. W. Jun. Release rates of ketoprofen from poloxamer gels in a membraneless diffusion cell. J. Pharm. Sci. 3:280–283 (1991).

    Google Scholar 

  7. W. E. Roorda, H. Bleyser, H. E. Junginger, and J. C. Leyte. Nuclear magnetic relaxation of water in hydrogels. Biomaterials 11:17–23 (1990).

    Google Scholar 

  8. J. A. Mollica, C. R. Rehm, J. B. Smith, and H. K. Govan. Hydrolysis of benzothiadiazines. J. Pharm. Sci. 60:1380–1384 (1971).

    Google Scholar 

  9. T. Fujita and A. Koshiro. Stability of flomoxef in aqueous solution and in intravenous admixture of 5% glucose infusion. Yakugaku Zasshi 108:777–787 (1988).

    Google Scholar 

  10. S. Mashimo, T. Umehara, and S. Kuwabara. Dielectric study on dynamics and structure of water bound to DNA using a requency range 107–1010 Hz. J. Phys. Chem. 93:4963–4967 (1989).

    Google Scholar 

  11. S. Mashimo and S. Kuwabara. The dielectric relaxation of mixtures of water and primary alcohol. J. Chem. Phys. 90:3292–3294 (1989).

    Google Scholar 

  12. N. Shinyashiki, N. Asaka, and S. Mashimo. Microwave dielectric study on hydration of moist collagen. Biopolymers 29:1015–1026 (1990).

    Google Scholar 

  13. H. Uedaira, M. Ikura, and H. Uedaira. Natural-abundance oxygen-17 magnetic relaxation in aqueous solutions of carbohydrates. Bull. Chem. Soc. Jpn. 62:1–4 (1989).

    Google Scholar 

  14. H. Lai and S. J. Schmidt. Water mobility and crystallization action of lactose-water systems by oxygen-17 and carbon-13 NMR. J. Food Sci. 55:1435–1440 (1990).

    Google Scholar 

  15. M. Ishimura and H. Uedaira. Natural-abundance oxygen-17 magnetic relaxation in aqueous solutions of apolar amino acids and glycine peptides. Bull. Chem. Soc. Jpn. 63:1–5 (1990).

    Google Scholar 

  16. H. Lai and S. J. Schmidt. Lactose crystallization in skim milk powder observed by hydrodynamic equilibria, scanning electron microscopy and 2H nuclear magnetic resonance. J. Food Sci. 55:994–999 (1990).

    Google Scholar 

  17. N. A. Armstrong, T. G. Mariam, K. C. James, and P. Kearney. The influence of viscosity on the migration of chloramphenicol and 4-hydroxybenzoic acid through glycerogelatin gels. J. Pharm. Pharmacol. 39:583–586 (1986).

    Google Scholar 

  18. T. G. Mariam, N. A. Armstrong, K. R. Brain, and K. C. James. The effect of gelatin grade and concentration on the migration of solutes into and through glycerogelatin gels. J. Pharm. Pharmacol. 41:524–527 (1988).

    Google Scholar 

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Authors and Affiliations

  1. National Institute of Hygienic Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158, Japan

    Sumie Yoshioka, Yukio Aso & Tadao Terao

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  1. Sumie Yoshioka
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  2. Yukio Aso
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  3. Tadao Terao
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Yoshioka, S., Aso, Y. & Terao, T. Effect of Water Mobility on Drug Hydrolysis Rates in Gelatin Gels. Pharm Res 9, 607–612 (1992). https://doi.org/10.1023/A:1015837723851

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  • DOI: https://doi.org/10.1023/A:1015837723851

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