ZEISS Microscopy Solutions for Drug Formulation Development

The majority of pharmaceutical powders are required to be less than 500 microns in size for ease of manufacture and biopharmaceutical performance. Powder behavior of particles in this size range spans cohesive to aeratable powders. Powder performance is not only dependent on the powder bulk density and micromeritic properties of individual particles, but also crucially the structuring of particles within the powder bed. Micromeritic assessment is also routinely performed using image analysis or particle sizing techniques such as laser diffraction analysis. However, there is a clear need for techniques that provide non-destructive microstructural information of pharmaceutical powder structures.

Microstructure (Q3) has emerged as an important topic of consideration in the regulatory science of topical drug products, opening alternative routes to demonstrate pharmaceutical equivalence between different batches of products or between brand and generic products. Yet the challenge in demonstrating equivalence of topical medicines is highlighted by Dry Powder Inhalers (DPI), where the pre-aerosolised formulation, DPI device and patients’ airflow all have an influence on the post-aerosolised formulation that is inhaled by the patient and reaches the lungs. Understanding how microstructure links to processing, properties and performance will enable the powder to be linked to efficacy, but a central part of this is the microstructural characterisation.

As part of the INFORM project, ZEISS and its partners have developed a non-destructive microstructural characterization technique using X-Ray microscopy for dry powder inhaler (DPI) formulations. XRM can provide unique microstructural insight at nano- and micro-scales, with a range of applications including complex inhalation blends. These techniques are showing promise to enable quantitative measurement of Q3 parameters of different blends and formulations in the asthma medication arena.