Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
J Pharm Sci. 2012 Jul;101(7):2398-407. doi: 10.1002/jps.23142. Epub 2012 Apr 12.
It was of interest to determine the solid-state acidity of chitin-metal silicate coprocessed excipients and to correlate this acidity to the chemical stability of cefotaxime sodium in the presence of the aforementioned excipients. The solid-state acidities of chitin aluminum silicate, chitin magnesium silicate, and chitin calcium silicate were determined by reflectance spectroscopy using structurally different dye molecules. The chemical stability of cefotaxime sodium was assessed at 50 °C in a 4% (w/v) slurry system in the pH range 6.6-10.5 and in the solid-state in the Hammett acidity range 6.1-7.8. The solid-state acidity was found to be reproducible because one or more structurally different dye molecules gave reliable solid-state acidity values. A significant discrepancy in pH stability profile of cefotaxime sodium between the solid-state and the slurry system was observed. Furthermore, chitin aluminum silicate showed minimum drug stability in the solid-state, close to where the maximum drug stability in the slurry was observed. This unexpected effect might be ascribed to the catalytic properties of chitin aluminum silicate. The slurry method was not able to predict efficiently the solid-state surface acidity and stability of cefotaxime sodium. Moreover, the solid-state chemical stability might be influenced by factors other than the solid-state acidity.
研究目的在于确定壳聚糖-金属硅酸盐共处理赋形剂的固态酸度，并将其与上述赋形剂存在时头孢噻肟钠的化学稳定性相关联。通过使用结构不同的染料分子的反射光谱法来确定壳聚糖铝硅酸盐、壳聚糖镁硅酸盐和壳聚糖钙硅酸盐的固态酸度。在 50°C 下，在 pH 值为 6.6-10.5 的 4%（w/v）浆料体系中和在 Hammett 酸度范围为 6.1-7.8 的固态下评估头孢噻肟钠的化学稳定性。由于一种或多种结构不同的染料分子给出了可靠的固态酸度值，因此发现固态酸度具有可重现性。在固态和浆料体系之间观察到头孢噻肟钠的 pH 稳定性曲线存在显著差异。此外，壳聚糖铝硅酸盐在固态下表现出最小的药物稳定性，接近于在浆料中观察到的最大药物稳定性。这种意外的影响可能归因于壳聚糖铝硅酸盐的催化特性。浆料方法不能有效地预测头孢噻肟钠的固态表面酸度和稳定性。此外，固态化学稳定性可能受到除固态酸度以外的因素的影响。
