Effect of solvent and temperature on solution-crystallized terfenadine

Abstract

The aim of this work was to understand the crystallization process of terfenadine in solution. Cooling of saturated solutions prepared at 50 • C at different temperatures, evaporating the solvent from nearly saturated solutions at a certain temperature, and exposing ethanol solutions of terfenadine to water vapour atmosphere were the techniques used for obtaining terfenadine specimens. The characterization of these specimens was carried out by thermal microscopy, differential thermal analysis, thermogravimetry and powder X-ray diffraction. Crystalline phases, amorphous solids, and solvates were identified. For the solvents used in the present study, the crystallinity degree of terfenadine decreases from ethanol-water to ethanol and from this to methanol. Decreasing the temperature promotes the formation of amorphous solid material; at low temperatures, methanol and ethanol solvates are also formed. Desolvation, following the terfenadine aggregation process in solution accounts for the different behaviour found for the solvents and for the effect of temperature on the structure. The role of the solvent as structure-mediator is explained on the grounds of the values previously published for the enthalpy of solution of terfenadine in the solvents under study.

Thermodynamic stability and transformation of pharmaceutical polymorphs

“…This fact makes the crystallization process complicated. We have observed that transformation behavior is influenced by temperature [5,6], additives [7][8], and solvents [9][10][11]. In the pharmaceutical industry, antisolvents are frequently used for crystallizations.…”