Assessment of incompatibilities between active pharmaceutical ingredient and pharmaceutical excipients is an important part of preformulation studies. The objective of the work was to assess the effect of moisture content of chitin calcium silicate of two size ranges (two specific surface areas) on the rate of degradation of cefotaxime sodium. The surface area of the excipient was determined using adsorption method. The effect of moisture content of a given size range on the stability of the drug was determined at 40°C in the solid state. The moisture content was determined at the beginning and the end of the kinetic study using TGA. The degradation in solution was studied for comparison. Increasing the moisture content of the excipient of size range 63-180 μm (surface area 7.2 m2/g) from 3.88 to 8.06% increased the rate of degradation of the drug more than two times (from 0.0317 to 0.0718 h-1). While an opposite trend was observed for the excipient of size range < 63 μm (surface area 55.4 m2/g). The rate of degradation at moisture content < 3% was 0.4547 h-1, almost two times higher than that (0.2594 h-1) at moisture content of 8.54%, and the degradation in solid state at both moisture contents was higher than that in solution (0.0871 h-1). In conclusion, the rate of degradation in solid should be studied taking into consideration the specific surface area and moisture content of the excipient at the storage condition and it may be higher than that in solution.
Keywords: cefotaxime sodium; chitin calcium silicate; degradation kinetics; moisture content; surface area.