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Enhancing the solubility of natural compound xanthotoxin by modulating stability via cocrystallization engineering
Jin-Yao Chen1, Hao Wu1, Chun-Yang Guo1
1State Key Laboratory of Bioreactor Engineering; Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education; Laboratory of Pharmaceutical Crystal Engineering & Technology, School of Pharmacy, East China University of Science and Technology, No. 130 Meilong Road, Shanghai 200237, China.
Abstract:
A comprehensive cocrystal study for the insoluble natural pharmaceutical compound xanthotoxin (XT) was conducted, in which xanthotoxin-para aminobenzoic acid (XT-PABA) and xanthotoxin-oxalic acid (XT-OA) cocrystals were obtained. The xanthotoxin cocrystals were characterized by powder X-ray diffraction, thermal analysis, and FT-IR spectra, and the crystal structures were determined by single-crystal X-ray diffraction. Crystal structures and thermal analysis showed that XT-OA was more stable than XT-PABA. Energy framework calculation indicated that H-bond and π···π interactions generated in XT-OA were stronger than that in XT-PABA and xanthotoxin. The powder dissolution experiments of xanthotoxin and its cocrystals suggested the XT-OA cocrystal might be applied as an alternative formulation of API, on account of its enhanced solubility and stability in the hydrochloric acid buffer solution (pH 1.2). The cocrystallization engineering can prolong the enhanced apparent solubility via modulating the stability.
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