Solubility and Permeability Improvement of Allopurinol by Cocrystallization

• Published in: Crystal growth & design Vol. 20; no. 8; pp. 5160 - 5168
• Main Authors: Dai, Xia-Lin, Yao, Jia, Wu, Chao, Deng, Jun-Hui, Mo, Yong-Hui, Lu, Tong-Bu, Chen, Jia-Mei
• Format: Journal Article
• Language: English
• Published: American Chemical Society 05.08.2020
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.0c00326

Allopurinol is a xanthine oxidase inhibitor with poor solubility and permeability, which severely limit its drug absorption following the administration of some dosage forms, such as tablets and rectal suppositories. To improve the physicochemical properties, three cocrystals of allopurinol with isonicotinamide (ALP-INA), piperazine (ALP-PIP), and 2,4-dihydroxybenzoic acid (ALP-24DHBZA) were successfully prepared by a slurry or liquid-assisted grinding method. The obtained cocrystal materials were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analyses and were subjected to dynamic vapor sorption, dissolution, and membrane permeability studies. ALP-INA showed solubility and diffusion/membrane permeability similar to those of the parent drug. In contrast, ALP-PIP exhibited improved diffusion/membrane permeability, and ALP-24DHBZA exhibited improved dissolution behavior, respectively. These results suggest that ALP-PIP and ALP-24DHBZA have the potential to be developed as new, more efficient formulations of allopurinol.