Nucleation and Crystallization Kinetics of Hydrated Amorphous Lactose Above the Glass Transition Temperature

Abstract

The crystallization kinetics of amorphous lactose in the presence and absence of seed crystals were investigated at 57.5% relative humidity. Isothermal crystallization studies were conducted gravimetrically in an automated vacuum moisture balance at several temperatures between 18 and 32°C. The crystallization rate constants were then determined from Johnson–Mehl–Avrami (JMA) treatment and isothermal activation energies were obtained from Arrhenius plots. Based on microscopic observations, a reaction order of 3 was used for JMA analysis. The nonisothermal activation energies were determined by differential scanning calorimetry using Kissinger's analysis. Isothermal activation energies for amorphous lactose with and without seed crystals were 89.5 (±5.6) kJ/mol and 186.5 (±17.6) kJ/mol, respectively. Nonisothermal activation energies with and without seed crystals were 71 (±7.5) kJ/mol and 80.9 (±8.9) kJ/mol, respectively. The similarity of the isothermal and nonisothermal activation energies for the sample with seeds suggested that crystallization was occurring by growth from a fixed number of preexisting nuclei. Markedly different isothermal and nonisothermal activation energies in the absence of seeds suggested a site-saturated nucleation mechanism, and therefore allowed calculation of an activation energy for nucleation of 317 kJ/mol.