Kiguchiya Akihito, Teraoka Reiko, Furubayashi Tomoyuki, Sakane Toshiyasu
Technology Research & Development Division, Sumitomo Pharma Co., Ltd.
Department of Pharmaceutical Technology, College of Pharmaceutical Sciences, Himeji Dokkyo University.
Yakugaku Zasshi. 2023;143(1):77-84. doi: 10.1248/yakushi.22-00152.
It is crucial to evaluate the photostability of drugs. However, it requires a longer period of time to evaluate the photodegradation of compounds because extended light exposure to the compound is required to detect photodegradation products with the help of the commonly utilized technique of chromatography. Therefore, a simple and easy approach to estimate the photostability of the compound is required particularly for the initial screening of the drug candidates. It was reported in our previous manuscript that, focusing on ultraviolet-visible (UV/vis) spectrometry, the area under the spectrum curve in the ultraviolet-A (UVA) range (AUSC) are closely related to the photodegradation of indomethacin polymorphs. In this study, the solid-state UV/vis absorption spectra of compound A polymorphs, indomethacin complexes and some small molecule compounds were determined and analyzed to check the applicability of this method. AUSC are closely related to the photodegradation of compound A polymorphs as well as indomethacin. On the contrary, no close relation was observed between AUSC of indomethacin complexes and their photodegradation. Additionally, the result indicated that the differences in their solid-state UV/vis absorption spectra were observed between photosensitive and photostable compounds. Photosensitive compounds show absorption in UVA range, while photostable compounds exhibit less absorption. In conclusion, the solid-state UV/vis absorption spectra of small molecular compounds might provide the key information on the photosensitivity.
评估药物的光稳定性至关重要。然而,评估化合物的光降解需要更长的时间,因为要借助常用的色谱技术检测光降解产物,就需要让化合物长时间暴露在光下。因此,尤其在对候选药物进行初步筛选时,需要一种简单易行的方法来估算化合物的光稳定性。我们之前的论文报道过,聚焦于紫外可见(UV/vis)光谱法,紫外-A(UVA)范围内的光谱曲线下面积(AUSC)与吲哚美辛多晶型物的光降解密切相关。在本研究中,测定并分析了化合物A多晶型物、吲哚美辛配合物和一些小分子化合物的固态UV/vis吸收光谱,以检验该方法的适用性。AUSC与化合物A多晶型物以及吲哚美辛的光降解密切相关。相反,未观察到吲哚美辛配合物的AUSC与其光降解之间存在密切关系。此外,结果表明,在光敏化合物和光稳定化合物之间观察到了它们固态UV/vis吸收光谱的差异。光敏化合物在UVA范围内有吸收,而光稳定化合物的吸收较少。总之,小分子化合物的固态UV/vis吸收光谱可能提供有关光敏性的关键信息。