Effects of experimental variables on purity determinations with differential scanning calorimetry

Abstract

A description is given of the influence of calculation procedure, heating rate, sample mass, particle size and atmosphere on the determination of molar purity by means of melting point depression with differential scanning calorimetry. This determination is the most important pharmaceutical application of DSC. Nine substances, melting in the region 100–250°C were studied and factorial designs were used. A large sample mass leads to high purity values because of thermal insulation within the powder bed. Values even greater than 100 mole% were found. Since at high heating rates thermal and thermodynamic equilibrium cannot be attained, there must be an upper limit on heating rate in purity determinations; this appeared to be 0.05 K sec−1. However, sometimes heating rates below this value influence both the purity value and pure melting point, T0.The particle size of the sample also affected its purity value. The effects could be explained in terms of thermal lags, decomposition and evaporation during melting, or sublimation before melting. Decrease of particle size may either lead to low purity values, due to concurrent increase in structural disorder, or to increase in purity values, due to the formation of aggregates by electrostatic forces. It was concluded that if trituration of samples before subjecting them to DSC analysis causes aggregate formation, purity values which are too high may result.Very large particles give lower purity values because of thermal gradients in the sample.