Crystallization of Terutroban Sodium Salt Hydrate from the Deliquescent State

Abstract

Terutroban sodium salt (Teru-Na) is a solid active pharmaceutical ingredient initially produced in its anhydrous form. The crystallization of a new dihydrate was established using liquid-assisted grinding and the liquid-liquid interface process. The stability of the Teru-Na crystalline phases was investigated as a function of temperature and relative humidity. A combination of analytical tools (spectroscopic, thermal, and vapor sorption analyses) highlighted the remarkable stability of the dihydrate, in particular under variable storage conditions. A rationalization of the stability hierarchy was proposed by means of phase diagrams.