Organic molecular salts of allopurinol with improved solubility

Allopurinol is considered to be one of the most effective medications, which is regularly prescribed to reduce urate level and treat chronic gout. The drug belongs to biopharmaceutics Classification System (BCS) class IV category with poor aqueous solubility and permeability. High-throughput solid-form screening of the active pharmaceutical ingredient for new binary solid forms was carried out in order to improve drug properties. Multicomponent solids with oxalic acid and maleic acid were obtained during liquid assisted grinding of equivalent stoichiometry. The novel binary systems were characterized by PXRD, FT-IR, DSC, TGA and SEM images. Vibrational spectroscopy was exploited to confirm the ionization states of the multicomponent systems. Thermal analysis indicates the new solid phases with the possibility of hydrates in the oxalate and maleate salts, which degraded to allopurinol after melting. Powder dissolution experiment was carried out on the drug and the salts in pH-1.2 (acidic) and pH-7 (phosphate buffer, neutral) medium, which suggests that salts improved dissolution up to 4 fold compared to the native drug. In both the aqueous medium, maleate salt exhibited higher dissolution rate compared to the oxalate salt, which is correlated with its (former) lower melting point and higher crystal surface area. (C) 2020 The Authors. Published by Elsevier Ltd.