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.