Summary

Milling-induced disordered (amorphous) material is highly energetic and a considerable portion of these particles significantly influences the cohesive and adhesive balance (CAB) of micronised particles. This behaviour results in varying fine particle fraction (FPF), which ultimately affects dry powder inhaler (DPI) performance. Milled particles are also heterogeneous in nature, they differ in particle size, shape, surface area and energetics. These characteristics make it challenging to produce stable DPI products without a deep understanding of the physical properties of milled and un-milled samples, their behaviour and control over their processing. It is reasonable for the regulatory authorities (e.g. FDA, MHRA) to seek a suitable analytical method to quantify amorphous content and they may assign limits for amorphous content in batches that are to be used for commercial purposes. Extensive work has been carried out on identifying and developing various techniques for amorphous content determination, which has added invaluable insights to this fundamental research. In the past, solution calorimetry methods have been developed using a 100mL vessel (containing 100mL solvent) only. A “Green Chemistry” approach – using a 25mL vessel (containing 25mL solvent) and therefore reducing solvent usage and waste – has not yet been developed. This study clearly demonstrates that given the right skills, knowledge and experience, a 25mL vessel can be used to obtain reproducible data and detect small levels of amorphous material within a crystalline bulk of formoterol fumarate dihydrate (FFD).

Key Message

By adopting a “Green Chemistry” approach, solution calorimetry can easily be used in a repeatable and robust manner to measure small level of amorphous content in a crystalline bulk for inhaled products.