Amorphous Lactose in Pharmaceuticals

ProUmid Application Note

Lactose is widely used in the pharmaceutical industry, e.g. as filler, binder, carrier substrate or diluent in tablets, capsules, or dry powder inhalators.

Lactose can be present in a crystalline or an amorphous state. The amorphous state is often caused process-related during spray- and freeze drying, grinding, compaction, extrusion or evaporation. While crystalline lactose is characterized by a regular arrangement of the molecules, the amorphous state commonly does not show any regular structures. Another characteristic of amorphous lactose is its hygroscopicity, which is associated with a high water-binding capacity. This promotes uncontrolled crystallization, combined with the release of crystallization water, if a critical moisture content is exceeded.

Application Note

Even low amorphous amounts can have negative effects on the product quality with regard to handling, dosage, and drug efficacy. This makes both the determination and the adjustment of the amorphous fraction an important task, e.g. for the specific adaption of process parameters or to assess the stability of lactose-containing products within the scope of quality assurance.

The DVS method is based on the higher moisture sorption affinity of amorphous compared to crystalline materials. In addition, water vapor sorption induces crystallization of the amorphous parts. Both kinetics of water vapor sorption and crystallization events can be followed by DVS experiments.

For quantitative determination of the amorphous content by DVS, several methods have been described in literature. The basic idea is to obtain a calibration curve by measuring the sorption behavior of powder mixtures with different ratios of amorphous to crystalline.