Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation DOI Open Access
Ioana Bâldea, Remus Moldovan, András Nagy

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13346 - 13346

Published: Dec. 12, 2024

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents controlled cocrystallization process by cooling for the 1:1 cocrystal Ketoconazole, an antifungal class II drug Fumaric acid coformer. was successfully set up following meta-stable zone width determination in acetone–water 4:6 (V/V) and pure ethanol. Considering optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering high yields 90% single phase revealed powder X-ray diffraction. Biological assays vitro showed improved viability oxidative damage over Ketoconazole on human dermal fibroblasts hepatocarcinoma cells; vivo, Wistar rats, increased oral bioavailability transient minor biochemical transaminases increases without histological liver alterations. Locally Balb C mice, it induced no epicutaneuous sensitization. A molecular docking conducted sterol 14α-demethylase (CYP51) enzyme from pathogenic yeast Candida albicans that interacts more compared indicating coformer enhances binding affinity ingredient.

Language: Английский

Comprehensive review of Hesperetin: Advancements in pharmacokinetics, pharmacological effects, and novel formulations DOI
Bocui Song,

Meihan Hao,

Shuang Zhang

et al.

Fitoterapia, Journal Year: 2024, Volume and Issue: 179, P. 106206 - 106206

Published: Sept. 8, 2024

Language: Английский

Citations

6
Uncovering Cocrystal Formation and Competition Mechanism of Polyhydroxy Natural Products: Cases of Quercetin, Hesperidin, Resveratrol, and Curcumin DOI

Detao Li,

Wenqian Chen, Limin Zhou

et al.

Crystal Growth & Design, Journal Year: 2024, Volume and Issue: 24(11), P. 4652 - 4667

Published: May 15, 2024

Understanding drug cocrystal formation and its competitive mechanism is important for improving the physicochemical properties of drugs. In this article, polyhydroxy natural products their mechanisms are discussed through experimental screening theoretical calculations. The conditions types cocrystals were determined based on efficient experiments product cocrystals. To investigate difficulty stability formation, carried out simultaneously. By simulation electrostatic potential surface molecules Hirshfeld crystals, mode hydrogen bonding within crystals was determined. strength assessed intermolecular interactions energy framework crystal structure. A "substitution model" constructed results calculations, which great significance prediction design provides a feasible solution

Language: Английский

Citations

4
Crystal structures and properties of two aromatic carboxylic acid-based medicinal salts of paliperidone DOI

Zheng Shen,

Jian Chen,

Jilong Ge

et al.

Structural Chemistry, Journal Year: 2023, Volume and Issue: 35(3), P. 967 - 975

Published: Oct. 30, 2023

Language: Английский

Citations

3
Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation DOI Open Access
Ioana Bâldea, Remus Moldovan, András Nagy

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13346 - 13346

Published: Dec. 12, 2024

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents controlled cocrystallization process by cooling for the 1:1 cocrystal Ketoconazole, an antifungal class II drug Fumaric acid coformer. was successfully set up following meta-stable zone width determination in acetone–water 4:6 (V/V) and pure ethanol. Considering optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering high yields 90% single phase revealed powder X-ray diffraction. Biological assays vitro showed improved viability oxidative damage over Ketoconazole on human dermal fibroblasts hepatocarcinoma cells; vivo, Wistar rats, increased oral bioavailability transient minor biochemical transaminases increases without histological liver alterations. Locally Balb C mice, it induced no epicutaneuous sensitization. A molecular docking conducted sterol 14α-demethylase (CYP51) enzyme from pathogenic yeast Candida albicans that interacts more compared indicating coformer enhances binding affinity ingredient.

Language: Английский

Citations

0