Pharmaceutical Technology Department, Faculty of Pharmacy, Jordan University of Science and Technology, P.O.Box 3030, Irbid, 22110, Jordan.
AAPS PharmSciTech. 2018 Apr;19(3):1337-1343. doi: 10.1208/s12249-017-0948-1. Epub 2018 Jan 16.
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 m/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). While an opposite trend was observed for the excipient of size range < 63 μm (surface area 55.4 m/g). The rate of degradation at moisture content < 3% was 0.4547 h, almost two times higher than that (0.2594 h) 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). 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.
评估原料药与药用辅料之间的不相容性是制剂前研究的重要组成部分。本工作的目的是评估两种粒径范围（两种比表面积）的壳聚糖钙硅的水分含量对头孢噻肟钠降解速率的影响。采用吸附法测定赋形剂的比表面积。在 40°C 下，在固态下测定给定粒径范围内的水分含量对药物稳定性的影响。在动力学研究的开始和结束时使用 TGA 测定水分含量。为了进行比较，还研究了溶液中的降解情况。粒径范围为 63-180 μm（比表面积为 7.2 m/g）的赋形剂的水分含量从 3.88%增加到 8.06%，使药物的降解速率增加了两倍多（从 0.0317 增加到 0.0718 h）。而粒径范围 <63 μm（比表面积为 55.4 m/g）的赋形剂则呈现出相反的趋势。在水分含量 <3%时，降解速率为 0.4547 h，几乎是水分含量为 8.54%时（0.2594 h）的两倍，且在两种水分含量下的固态降解速率均高于溶液中的降解速率（0.0871 h）。总之，在考虑到储存条件下赋形剂的比表面积和水分含量的情况下，应研究固体的降解速率，其可能高于溶液中的降解速率。
