α-Lactose monohydrate - new insights into physicochemical response to temperature and humidity exposure

Environmental relative humidity (RH) and temperature (T) are known to be promoters of physicochemical changes in pharmaceutical grade lactose, either in controlled (supervised conditioning), or uncontrolled (during transit and repository storage) scenarios. Comprehensive knowledge of this excipient's material characteristics prior to its use in formulation development is therefore a fundamental requirement. In this work, two kinetic processes are identified and characterized, namely crystallization and relaxation. The former is driven mainly by recrystallization of amorphous surface regions and may lead to particle aggregation and apparent growth, while the latter is explained by long-term structural reorganization and smoothing of particle surfaces. By quantitatively determining changes in amorphicity, particle size distribution, specific surface area, crystal structure and thermal properties, a two-step fitting kinetic model is proposed which captures experimental trends. The results show that while the crystallization component and initial relaxation is mainly driven by relative humidity, the long-term relaxation, which has a continuous impact on specific surface area, is less dependent on temperature and humidity and is only partially related to changes in amorphicity and apparent particle size.