Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole Through Crystal Engineering

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Oct 28

PMID 37895820

Authors

Hongmei Yu

Li Zhang

Meiju Liu

Dezhi Yang

Guorong He

Baoxi Zhang

Ningbo Gong

Yang Lu

Guanhua Du

Affiliations

Soon will be listed here.

Abstract

To improve the solubility and dissolution rate of the BCS class II drug ketoconazole, five novel solid forms in 1:1 stoichiometry were obtained upon liquid-assisted grinding, slurry, and slow evaporation methods in the presence of coformers, namely, glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acids. Single-crystal X-ray diffraction analysis revealed that the hydroxyl/carboxylic acid. . .N-imidazole motif acts as the dominant supramolecular interaction in the obtained solid forms. The solubility of ketoconazole in distilled water significantly increased from 1.2 to 2165.6, 321.6, 139.1, 386.3, and 191.7 μg mL in the synthesized multi-component forms with glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acid, respectively. In particular, the cocrystal form with glutaric acid showed an 1800-fold solubility increase in water concerning ketoconazole. Our study provides an alternative approach to improve the solubility and modify the release profile of poorly water-soluble drugs such as ketoconazole.

Citing Articles

Solubilization techniques used for poorly water-soluble drugs.

Xie B, Liu Y, Li X, Yang P, He W Acta Pharm Sin B. 2024; 14(11):4683-4716.

PMID: 39664427 PMC: 11628819. DOI: 10.1016/j.apsb.2024.08.027.

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