Version 1
: Received: 15 November 2023 / Approved: 15 November 2023 / Online: 16 November 2023 (11:33:57 CET)
How to cite:
Wang, Z.; Shen, S.; Peng, J.; Wu, D.; Liu, X.; Deng, Y.; Shi, X.; Su, W. Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility. Preprints2023, 2023111082. https://doi.org/10.20944/preprints202311.1082.v1
Wang, Z.; Shen, S.; Peng, J.; Wu, D.; Liu, X.; Deng, Y.; Shi, X.; Su, W. Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility. Preprints 2023, 2023111082. https://doi.org/10.20944/preprints202311.1082.v1
Wang, Z.; Shen, S.; Peng, J.; Wu, D.; Liu, X.; Deng, Y.; Shi, X.; Su, W. Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility. Preprints2023, 2023111082. https://doi.org/10.20944/preprints202311.1082.v1
APA Style
Wang, Z., Shen, S., Peng, J., Wu, D., Liu, X., Deng, Y., Shi, X., & Su, W. (2023). Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility. Preprints. https://doi.org/10.20944/preprints202311.1082.v1
Chicago/Turabian Style
Wang, Z., Xiangjun Shi and Weike Su. 2023 "Study on Novel Solid-State Forms of Sorafenib with Advantages in Terms of Solubility" Preprints. https://doi.org/10.20944/preprints202311.1082.v1
Abstract
The development of solid-state forms of drugs is an effective mean of solubility enhancement. In this study, two polymorphs named form C, form D, and two co-crystals of sorafenib (SF) with oxalic acid (SF-OA) and malonic acid (SF-MA), by evaporation and slurry method, have been developed and characterized. The single-crystal X-ray diffraction results showed that the structure of form C was similar to of form I. It had similar cellular parameters, but different arrangement of stacking due to π-π conjugation. The drug molecules in SF-OA underwent torsional folding through four hydrogen bonds of intermolecular and intramolecular. The solubility performance of solid-state forms improved significantly. Compared with form I, form C and form D were 1.59, 1.49 times at pH 1.2 HCl, 1.59, 1.87 fold at pH 6.8 PBS. In particular, the SF-OA and SF-MA increased the apparent solubility of SF at pH 1.2 by 8.3 and 6.4 times, at pH 6.8 by 4.0 and 4.5 times respectively. The dissolution mechanisms were analyzed. New solid-state forms showed strong stability at storage conditions of 40 °C/75% RH and 60 °C/0% RH. Notably, the crystal of SF preferred to transform in mixed solvents, and the formation of co-crystals confirmed the ∆pKa rule.
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
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