Coamorphous Lurasidone Hydrochloride–Saccharin with Charge-Assisted Hydrogen Bonding Interaction Shows Improved Physical Stability and Enhanced Dissolution with pH-Independent Solubility Behavior

Abstract

Recently, coamorphous systems, composed of a drug and a guest molecule, have gained increasing interest, due to their ability to overcome limitations associated with amorphous drug alone. In this study, a single-phase coamorphous form of lurasidone hydrochloride (LH) (a water-insoluble atypical antipsychotic agent with pH-dependent solubility) with saccharin (SAC) in a 1:1 molar ratio was obtained and characterized by differential scanning calorimetry and powder X-ray diffraction. Peak shifts in the Fourier transform infrared spectra indicated the formation of charge-assisted hydrogen bonds between the N+-H group of LH and the C═O group of SAC. In comparison to crystalline LH, amorphous LH showed similar solubility and temporary improvement in the intrinsic dissolution rate and supersaturated dissolution, while coamorphous LH-SAC exhibited greatly improved solubility with pH-independent solubility behavior in a pH range of 2–5.5, as well as a persistent enhanced intrinsic dissolution rate and supersaturated dissolution. In addition, coamorphous LH-SAC showed superior physical stability compared to amorphous LH under the long-term storage condition. The coamorphization effect and charge-assisted hydrogen bond in coamorphous LH-SAC were speculated to be responsible for the above phenomena by prohibiting the recrystallization of LH.