Monitoring the Dissolution Behavior of Novel Pharmaceutical Cocrystals Consisting of Antimalarial Drug Artemisinin with Probe-Type Low-Frequency Raman Spectrometer.

IF 2.2 3区 化学 Q2 INSTRUMENTS & INSTRUMENTATION
Takayuki Kudo, Soichiro Miura, Kazuhiko Takatori, Varin Titapiwatanakun, Vasanthi Palanisamy, Katsuhiko Yamamoto, Yukihiro Ikeda, Toshiro Fukami
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Abstract

Artemisinin (ART) is a most promising antimalarial agent. However, its low aqueous solubility limits its oral absorption, resulting in low bioavailability. In this study, we have successfully discovered a novel cocrystal with 2-methyl resorcinol (ART-2MRE) providing improved solubility compared with a previously reported cocrystal with resorcinol (ART-RES). Single crystal X-ray structure analysis revealed that the ART-2MRE cocrystal was composed of ART and 2MRE in a molar ratio of 2 : 1. Though the ART-2MRE and ART-RES cocrystals were found to have similarities in their crystal structures, with one layer of a cocrystal former and two layers of ART arranged in alternating rows, the ART-2MRE cocrystal showed higher dissolution rate than ART-RES cocrystal. In situ real-time low-frequency (LF) Raman monitoring and powder X-ray diffraction (PXRD) measurements of the crystals during the dissolution test proved useful to investigate the dissolution behavior of the cocrystals. Low-frequency Raman monitoring revealed that as dissolution progressed, there was a continuous shift from the peak unique to the ART-2MRE cocrystal to the peak unique to the ART stable form. Similar observations were obtained in PXRD measurements as well. Furthermore, experiments were conducted by adding a polymer to the dissolution test solution to investigate the dissolution behavior under supersaturation, indicating the possibility of differences in the dissolution behavior between the ART-2MRE cocrystal and ART-RES cocrystal. Understanding the dissolution behavior from cocrystals is essential in developing cocrystals.

用探针式低频拉曼光谱仪监测包含抗疟药青蒿素的新型药用复方晶体的溶解行为
青蒿素(ART)是一种最有前途的抗疟药物。然而,其较低的水溶性限制了其口服吸收,导致生物利用度较低。在这项研究中,我们成功地发现了一种与 2-甲基间苯二酚的新型共晶体(ART-2MRE),与之前报道的与间苯二酚的共晶体(ART-RES)相比,这种共晶体的溶解度更高。单晶 X 射线结构分析表明,ART-2MRE 共晶体由 ART 和 2MRE 组成,摩尔比为 2 :1.虽然 ART-2MRE 和 ART-RES 共晶体的晶体结构相似,都是一层共晶体前体和两层 ART 交替排列,但 ART-2MRE 共晶体的溶解率高于 ART-RES 共晶体。事实证明,在溶解测试过程中对晶体进行原位实时低频拉曼监测和粉末 X 射线衍射 (PXRD) 测量有助于研究共晶体的溶解行为。低频拉曼监测显示,随着溶解的进行,ART-2MRE 共晶体特有的峰值不断向 ART 稳定型特有的峰值转移。在 PXRD 测量中也获得了类似的观察结果。此外,还通过在溶解测试溶液中添加聚合物来研究过饱和状态下的溶解行为,这表明 ART-2MRE 共晶体和 ART-RES 共晶体的溶解行为可能存在差异。了解共晶体的溶解行为对开发共晶体至关重要。
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来源期刊
Applied Spectroscopy
Applied Spectroscopy 工程技术-光谱学
CiteScore
6.60
自引率
5.70%
发文量
139
审稿时长
3.5 months
期刊介绍: Applied Spectroscopy is one of the world''s leading spectroscopy journals, publishing high-quality peer-reviewed articles, both fundamental and applied, covering all aspects of spectroscopy. Established in 1951, the journal is owned by the Society for Applied Spectroscopy and is published monthly. The journal is dedicated to fulfilling the mission of the Society to “…advance and disseminate knowledge and information concerning the art and science of spectroscopy and other allied sciences.”
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