Exploring New Solid Forms of Antirheumatic Drug Hydroxychloroquine: Novel Salts with Sustained-Release Performance

Hydroxychloroquine sulfate is a common drug for the treatment of rheumatoid arthritis. However, the disadvantage of this drug is that it needs to be taken continuously for 3-6 months to be effective and compliance of patients is poor. In this work, four new salt forms of hydroxychloroquine are successfully prepared whose crystal structures and properties are confirmed by a series of solid-state characterization methods, including infrared spectroscopy, single crystal X-ray diffraction, powder X-ray diffraction, thermal analysis, and dynamic vapor sorption analysis. The hygroscopicity, stability, equilibrium solubility, and intrinsic dissolution rate of the four new salts are also tested. The moisture absorption, solubility, and intrinsic dissolution rate of newly prepared salts are significantly reduced, and the dissolution rates of 1-hydroxy-2-naphthoate and 1,5-naphthalenedisulfonate salts are only 1/158 and 1/335 of that of the therapeutically used sulfates, respectively. It is expected that they are potentially useful to be developed into a sustained-release formulation, which can greatly improve the dosing compliance for rheumatoid arthritis treatment. In this work, four salt forms of hydroxychloroquine are prepared. Their structures are confirmed by solid-state characterization and their physicochemical properties are tested in vitro. Two of them appear to be suitable for extended-release drug delivery study. image