Determination of porosity and pore-size distribution of aspirin tablets relevant to drug stability.

Total porosity and pore-size distribution of aspirin tablets prepared from aspirin, starch USP, and precipitated colloidal silicon dioxide were determined using mercury porosimetry. The model represented a hydrolyzable drug substance in combination with simple excipients. The role of starch and silicon dioxide on the microstructure of the tablets was investigated, as was the chemical stability of various systems. In general, the porosity of tablets containing a constant quantity of starch increased linearly with silicon dioxide concentration. Examination of the pore-size distribution, however, revealed that a low concentrations silicon dioxide functioned primarily to reduce the size and volume of coarse pores representing the spaces between the agglomerates of starch and aspirin particles. This effect was optimum at 3%. A further increase in silicon dioxide concentration produced tablets with relatively larger pore sizes. Studies of changes in the porosity characteristics of tablets as influenced by water vapor over time showed distinct differences in this complex parameter. A unique trend in the change of the pore-size distribution was noted with tablets containing 3% silicon dioxide. These observations are discussed relative to the stability of aspirin tablets in which this concentration of silicon dioxide produced a maximum stabilizing effect.

Rapid determination of nitroglycerin volatility using thermogravimetric analysis.

The effect of selected tablet components on the volatility of nitroglycerin from compressed sublingual tablets was studied by thermogravimetric analysis. The results, confirmed by chemical analyses, showed that nitroglycerin volatility is significantly reduced by the use of povidone USP and microcrystalline cellulose NF in tablet formulations. In general, the stabilizing effect of these materials was dependent on the presence and the concentration of each other. These studies demonstrated the utility of thermogravimetric analysis as a rapid and reliable means of screening nitroglycerin formulations for stability purposes.

Stabilized compressed nitroglycerin tablets.

A stabilized compressed nitroglycerin tablet, containing microocrystalline cellulose NF and providone NF as stabilizing agents, was formulated. Bioavailability and physical tests were conducted on the compressed tablet and two leading brands of molded tablets. There was no difference in the mean pulse rate between a molded tablet formulation and the compressed tablet in a crossover study using 10 human volunteers and three tablet strengths, 0.3, 0.4, and 0.6 mg. The compressed tablet was most uniform when tested according to the USP method for weight variation and content uniformity. Various tests for nitroglycerin loss due to volatility, i.e., open dish test, thermogravimetric analysis, and simulated in-use test, all indicated that the stabilized compressed tablet was substantially more stable than partially stabilized or unstabilized molded tablets.