Sublimation measurements of pharmaceutical compounds by isothermal thermogravimetry

Procedures for measuring sublimation rates of pharmaceutical compounds by isothermal thermogravimetry are discussed. Experimental data was obtained using the Mettler TA4000 thermogravimetric system. The sublimation rate is measured directly from the mean weight loss per unit time in the linear region of the monitored TG profile at a set isothermal temperature. This data when fitted to the Arrhenius equation yields the sublimation enthalpy. For the benzoic acid reference, the enthalpy so calculated is 99% of the value obtained from direct vacuum TG measurements. Thermal degradation in the solid state or pre-melting can effect a departure from the characteristic linear mass loss-time sublimative profile. Data pertaining to several established Merck drugs is discussed. Examples where loss of residual solvent, onset of thermal degradation and pre-melting phenomena affect the measurement, are presented.