Pharmaceutical Studies on Hydrates of AM-715 : Physical Characteristics and Intestinal Absorption

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Abstract
The presence of 3 kinds of hydrates of Am-715 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)-3-quinolinecarboxylic acid] was confirmed by elemental analysis, Karl-Fisher method, thermogravimetric analysis, differential scanning calorimetry, IR spectroscopy and X-ray diffractometry. Anhydrous AM-715 was not hygroscopic under less than 36% of relative humidity, but easily transformed to 5/2-hydrate over 62-78% of relative humidity and 5-hydrate above 94% of relative humidity, at 40.degree. C. Anhydrous AM-715 was transformed to 5/2-hydrate with 1st-order kinetics and 5/2-hydrate was dehydrated according to 1st-order kinetics with an activation energy of dehyration of 22 kcal/mol. The 5/2-hydrate was converted to 5-hydrate more slowly than anhydrous AM-715. Dissolution rates were determined in water by using tape procedure, showing a slight difference between anhydrous AM-715 and its hydrates. To determine the effect of hydration on bioavailability, the serum levels in dogs were measured after oral administration. There were no significant differences among bioavailability of anhydrous AM-715, its 5/2-hydrate and 5-hydrate.

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