Phase solubility diagrams and energy surface calculations support the solubility enhancement with low hygroscopicity of Bergenin: 4-Aminobenzamide (1: 1) cocrystal

Hongji Liu, Jinju Nie, H. C. Stephen Chan, Hailu Zhang, Liang Li, Hongqing Lin, Henry H.Y. Tong, Ande Ma, Zhengzheng Zhou

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Herein, we reported a new bergenin: 4-aminobenzamide (BGN-4AM) cocrystal with significantly enhanced solubility and low hygroscopicity probed from two aspects such as phase solubility diagrams and theoretical calculations. Compared with anhydrous BGN, BGN-4AM solubilities in water and different buffer solutions (pH = 1.2, 4.5, 6.8) increase significantly. It is noted that BGN-4AM solubility in pH = 6.8 buffer solution presents 32.7 times higher than anhydrous BGN. Interestingly, BGN-4AM (0.31 ± 0.07%) showcases lower hygroscopicity than anhydrous BGN (9.31 ± 0.16%). The predicted and experimental solubilities agree with each other when considering solubility product (Ksp) and solution binding constant (K11) in phase solubility diagrams, indicating the solution complexes formation occurs. Further crystal surface-water interactions and Bravais, Friedel, Donnay-Harker (BFDH) analyses based on Density Functional Theory with dispersion correction (DFT-d) methods support the enhanced solubility. The water probe demonstrates an average interaction energy of −6.48 kcal/mol on the 002 plane of BGN-4AM, and only −5.47 kcal/mol on the 011 plane of BGN monohydrate. The lower lattice energy of BGN-4AM guarantees its lower hygroscopicity than BGN monohydrate. BGN-4AM with enhanced solubility and low hygroscopicity can be a potential candidate for further formulation development.

Original languageEnglish
Article number120537
JournalInternational Journal of Pharmaceutics
Volume601
DOIs
Publication statusPublished - 15 May 2021

Keywords

  • Bergenin
  • Cocrystal
  • DFT
  • Hygroscopicity
  • Solubility

Fingerprint

Dive into the research topics of 'Phase solubility diagrams and energy surface calculations support the solubility enhancement with low hygroscopicity of Bergenin: 4-Aminobenzamide (1: 1) cocrystal'. Together they form a unique fingerprint.

Cite this