University of Helsinki, FI-00014, Finland.
Int J Pharm. 2011 Sep 15;416(1):242-51. doi: 10.1016/j.ijpharm.2011.06.050. Epub 2011 Jul 7.
Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30°C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.
在 30°C/56%RH 的应激条件下储存 3 个月前后，研究了基于有序介孔硅材料 MCM-41 和 SBA-15 的高吲哚美辛（IMC）含量制剂的稳定性。总体而言，储存后样品的物理稳定性令人满意。然而，在化学稳定性方面存在一些问题，特别是对于基于 MCM-41 的样品。从药物在应激后 HPLC 负载度的降低以及应激样品中药物 HPLC 图谱中观察到的额外峰可以明显看出稳定性问题。与块状结晶 IMC 相比，介孔制剂在 pH 1.2 时的药物释放速度较快。在应激后，释放曲线仍然相似。当 pH 值从 1.2 升高到 6.8 时，实现了更快且接近完全的 IMC 释放。据我们所知，这是首例关于介孔硅药物制剂中药物化学稳定性问题的报告。目前的结果鼓励进一步研究影响介孔硅 MCM-41 和 SBA-15 制剂中药物化学稳定性的因素，以实现其在口服药物递送中的潜力。
