PHYSICO-CHEMICAL FACTORS AFFECTING THE SURFACE AREA AND PORE SIZE DISTRIBUTION OF COMPRESSED PHARMACEUTICAL SYSTEMS

HASAN GUCLUYILDIZ, Purdue University

Abstract

A study was undertaken to directly examine the surface area and porosity characteristics of compressed pharmaceutical systems and to elucidate the influence of some physico-chemical factors of these parameters. The BET nitrogen and water vapor surface areas of aluminum hydroxide dried gel (AHDG) tablets were determined and correlated with compression pressure. The theoretical treatment used to relate the total porosity of AHDG tablets with compression pressure indicated that consolidation of the powder is achieved by plastic deformation. In an attempt to characterize the pore size distribution of AHDG tablets the utility of the adsorption and mercury intrusion methods was explored. The limitations and the inherent assumptions of these techniques were critically evaluated. The mercury intrusion method permitted a direct examination of porosity characteristics attained in tablets as a function of compression pressure. The major differential effect of compression was observed to be a substantial increase in pore volume in the fine pore size regions of the pore size distribution, while the volume of coarse pores were virtually unaffected. Studies were also conducted, relative to aspirin stability, to determine the effect of colloidal silica on the porosity characteristics of aspirin-silica tablets prepared from aspirin, silica, and a constant concentration of starch. It was found that under constant compression conditions the total porosity of tablets was directly proportional to the silica concentration. Examination of the pore size distribution by the mercury intrusion method allowed a complete elucidation of the microstructural changes produced by the presence of silica in tablets. It was noted that silica functioned primarily to reduce the size and volume of coarse pores representing the spaces between the aggregations of starch and aspirin particles. This effect was found to be optimum at a concentration level of 3%. Determination of the changes in the pore size distribution of aspirin-silica tablets, exposed to a condition of elevated temperature and water vapor pressure, revealed distinct differences in this parameter as functions of silica concentration and periods of exposure. These results were explained in terms of the accessibility of water vapor and the condensed liquid to starch grains and to the aspirin surface. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI

Degree

Ph.D.

Subject Area

Pharmacology

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