Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Molecules. 2022 Nov 29;27(23):8322. doi: 10.3390/molecules27238322.
The chemical stability of diphenhydramine (DIPH), azelastine (AZE) and bepotastine (BEPO) was examined in solutions and solids. The drugs were subjected to high temperature (70 °C for 35 h) or UV/VIS light (18.902−94.510 kJ/m2) at pH 1−13, to examine their percentage degradation and kinetics of degradation. Further, the stability of solid DIPH, AZE and BEPO was examined in the presence of excipients of different reactivity, i.e., citric acid (CA) and polyvinyl alcohol (PVA) under high temperature/high humidity (70 °C/80% RH) or UV/VIS light (94.510 kJ/m2). Under high temperature, DIPH degraded visibly (>19%) at pH 1 and 4, AZE was shown stable, while the degradation of BEPO was rather high (>17%) in all pH conditions. Under UV/VIS irradiation all the drugs were shown labile with degradation in the range 5.5−96.3%. As far as the solid mixtures were concerned, all drugs interacted with excipients, especially under high temperature/high humidity or UV/VIS light. As a result, DIPH, AZE and BEPO were compared in terms of their stability, with regard to their different structures and acid/base properties. All these results may be helpful for manufacturing, storing and applying these drugs in their topical (skin, nasal and ocular), oral and injectable formulations.
本文研究了盐酸苯海拉明（DIPH）、氮卓斯汀（AZE）和贝他斯汀（BEPO）在溶液和固体中的化学稳定性。在 pH 值为 1-13 的条件下，药物分别经受高温（70°C 下 35 小时）或 UV/VIS 光（18.902-94.510 kJ/m2）照射，以检查其降解百分比和降解动力学。此外，还在高温/高湿度（70°C/80% RH）或 UV/VIS 光（94.510 kJ/m2）条件下，考察了固体 DIPH、AZE 和 BEPO 与不同反应性赋形剂（如柠檬酸（CA）和聚乙烯醇（PVA））共存时的稳定性。在高温下，DIPH 在 pH 值为 1 和 4 时明显降解（>19%），AZE 则稳定，而 BEPO 的降解率则相当高（>17%），所有 pH 值条件下均如此。在 UV/VIS 照射下，所有药物均不稳定，降解率在 5.5-96.3%之间。就固体混合物而言，所有药物都与赋形剂相互作用，尤其是在高温/高湿度或 UV/VIS 光下。因此，考虑到它们不同的结构和酸碱性质，对 DIPH、AZE 和 BEPO 的稳定性进行了比较。这些结果可能有助于这些药物在局部（皮肤、鼻腔和眼部）、口服和注射制剂中的制造、储存和应用。
