Phase solubility diagrams and energy surface calculations support the solubility enhancement with low hygroscopicity of Bergenin: 4-Aminobenzamide (1: 1) cocrystal.
Int J Pharm
; 601: 120537, 2021 May 15.
Article
em En
| MEDLINE
| ID: mdl-33781883
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.
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01-internacional
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MEDLINE
Assunto principal:
Solubilidade
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China