Application of a humidity-mediated method to remove residual solvent from crystal lattice

Abstract

We previously reported a humidity-mediated method to effectively remove methanol from the crystal lattice of 3',5'-cyclic monophosphate sodium (cAMPNa) methanol trihydrate, converting it to the pentahydrate without changing its inherent orthorhombic packing mode, and preserving its stability. In this paper, we expand this approach to the removal of residual solvents from l-lysine l-glutamate salt and inosine-5'-monophosphate, and contrast the humidity-mediated method with a solvent-mediated method and a conventional drying method. The packing density of the products obtained from the humidity-mediated method were ∼60% higher than those of the products obtained from the solvent-mediated method, and their stability is ∼5-10% higher than those obtained from the solvent-mediated and traditional drying methods. Furthermore, the humidity-mediated method can remove residual methanol more completely. Therefore, the humidity-mediated method can be regarded as a simple and effective route to eliminate residual solvent from crystal lattice for some crystal products, especially residual methanol.

Keywords: Crystal lattice; Humidity-mediated method; Hydrates; Inosine-5′-monophosphate; Residual solvent; Solvates; l-lysine l-glutamate salt.