Abstract
Safinamide (SAF) is an anti-Parkinson’s disease (PD) drug that has selective monoamine oxidase type-B (MAO-B) inhibition activity. In 2017, SAF was approved by the U.S. Food and Drug Administration (FDA) as safinamide mesylate (SAF-MS, marketed as Xadago). Owing to its poor solubility in water, SAF is a Biopharmaceutics Classification System BCS Class II compound. In this study, four salts of safinamide (with hydrochloric acid (HCl), hydrobromic acid (HBr), and maleic acid (MA)) were obtained and characterized using single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetry (TG). The solubility and dissolution rate of all salts were systematically studied in water and phosphate buffer (pH 6.86) solutions. The accelerated stability tests indicated that all salts, except SAF-MA, had good stability under high humidity conditions.
Highlights
Approximate 40% of drug candidates fail during the late stages of drug discovery owing to their poor water solubility and intrinsic dissolution rate (IDR) [1,2]
Safinamide is a Biopharmaceutics Classification System (BCS) II drug with low solubility and high permeability, and it has been commercialized in its salt form, safinamide mesylate and was approved, in 2017, by the U.S Food and Drug Administration
A series of conformers containing organic and inorganic acids were used to interact with safinamide (Supplementary Materials Table S1), and four novel salts of safinamide with hydrochloric acid (HCl), hydrobromic acid (HBr), and maleic acid (MA) were prepared and characterized, and their solubilities, IDRs and stability were evaluated
Summary
Approximate 40% of drug candidates fail during the late stages of drug discovery owing to their poor water solubility and intrinsic dissolution rate (IDR) [1,2]. Many methods have been developed, such as solid dispersion [3], nanocrystals [4], cocrystal [5,6,7], salts [8,9,10], to improve the water solubility of poorly soluble drugs [11]. There have been no relevant studies undertaken on the crystal structure and physicochemical properties of cocrystals and salts of safinamide. A series of conformers containing organic and inorganic acids were used to interact with safinamide (Supplementary Materials Table S1), and four novel salts of safinamide with hydrochloric acid (HCl), hydrobromic acid (HBr), and maleic acid (MA) were prepared and characterized, and their solubilities, IDRs and stability were evaluated.
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