QUANTITATIVE EVALUATION OF PHARMACEUTICAL EFFERVESCENT SYSTEMS
Abstract
The study of rapidly reacting, effervescent, carbon dioxide generating chemical compositions in compacted form was undertaken to develop effervescent pharmaceutical systems with improved stability properties and/or reduced moisture sensitivity, to permit manufacture under less rigorously controlled environmental conditions. The study was designed as a series of consecutive screening procedures. The first screen, that of materials hygroscopicity, eliminated materials which would attract more than a fixed amount of moisture into the system and destroy the reactivity. The second screen, applied in two stages, was a reactivity test utilizing two new test methods to permit dynamic measurements of fast reacting effervescent materials. The first method monitored carbon dioxide pressure generation during the effervescent reaction in a plastic pressure vessel fitted with a pressure gage. The second method monitored weight loss, attributed to carbon dioxide loss to the atmosphere, by means of a double cantilever beam and an electromagnetic proximity transducer. Characterization of the effervescent reaction was accomplished by determining the total carbon dioxide weight loss, dissolution time of the effervescent system and the pressure generated. Further characterization was accomplished by plotting the logarithmic relationship between carbon dioxide weight loss and time from which a pseudo first order rate constant and induction period were calculated. A stability study was applied to the best effervescent systems surviving the initial screening tests. Stability was monitored by measuring the loss of reactivity with time as well as physical changes with time, notably tablet density and porosity. The stability study included the following independent variables; manufacturing conditions, compression pressures, tablet formulations, storage conditions and storage time. It was found that the manufacturing condition factor had little effect on the stability of effervescent tablets when using non-hygroscopic materials, selected by the hygroscopicity screen. While compression pressure had no effect on effervescent tablet stability, the tablet formulation, storage condition and storage time were definite factors in effervescent stability. Mercury intrusion porosimetry proved to be a useful tool to elucidate pore structure changes in effervescent tablets. A correlation was found between the tablet reactivity index and the tablet porosity index used in this study. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Pharmaceuticals
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