Implementation and validation of the thermogravimetric method for the determination of equilibrium vapour pressure values and sublimation enthalpies of frozen organic formulations used in drug freeze–drying processes

• Published in: Chemical engineering research & design Vol. 89; no. 12; pp. 2606 - 2612
• Main Authors: Bogdani, Eni, Daoussi, Rim, Vessot, Séverine, Jose, Jacques, Andrieu, Julien
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2011; Elsevier
• Subjects: Analytical chemistry; Applied sciences; Chemical engineering; Chemical Sciences; Exact sciences and technology; Freeze–drying; Sublimation enthalpies; Sublimation vapour pressure; Tert-butanol; Thermogravimetry; Sublimation vapour pressure; Freeze–drying; Tert-butanol; Sublimation enthalpies; Thermogravimetry; Freeze drying; Vapor pressure; Enthalpy; Sublimation; Modeling; Dynamic conditions; Azeotropic mixture; Eutectic; Liquid vapor equilibrium; Thermodynamic properties; Phase equilibrium; Freeze-drying; ACID; BINARY-MIXTURES; BUTYL ALCOHOL; CURVES; WATER
• ISSN: 0263-8762; 1744-3563
• DOI: 10.1016/j.cherd.2011.05.004

The modelling of the sublimation step needs the knowledge of basic thermodynamic properties as the equilibrium solid–vapour pressures and the sublimation enthalpies. Unfortunately these thermodynamic properties are generally missing in the literature. Tert-butanol (TBA) co-solvent has been used largely as solvent in freeze–drying formulation. Thus, in the present study, we have determined the equilibrium values of vapour pressures (solid–vapour and liquid–vapour equilibrium) and sublimation enthalpies of pure TBA and for its eutectic mixture with water, namely the 90% (w/w) TBA + 10% (w/w) mixture, by using two different and comparative methods: the Thermogravimetric Method (TG Method) and the Static Method. TG experiments were conducted in dynamic conditions in a temperature range from −30 °C to 80 °C. Both methods led to similar values with a relative deviation less than 2%. This validation proved that the TG method is a rapid, reliable and precise technique for the determination of solid/vapour and liquid/vapour equilibrium pressures for pure substances or for co-solvent + water mixtures at eutectic/azeotropic compositions.