Formulating microstructural equivalence: A route to consistent scale-up of medicine manufacture

Medicine development requires not only identification of an active pharmaceutical ingredient (API), but it also requires the design of a product formulation that can be manufactured at scale with sufficient quality, stability and efficacy to deliver consistent performance when used by patients. Decisions on formulation design must often be made when supply of API is very limited, and yet formulation and manufacturability must be achieved throughout the development and product manufacturing lifecycle. International medicines regulatory agencies (i.e. European Medicines Agency, USA Food and Drug Administration) have published regulatory guidelines that request characterization of product microstructure as a route to demonstrating equivalence between batches and also between generic and innovator product. However, non-destructive analytical techniques for microstructural assessment are lacking to-date.

 

In the current research, we propose a new approach to the development of medicinal products, focusing particularly on dry powder inhalation formulations. This approach termed "Formulating for Microstructural Equivalence" has manufacturability and scale-up potential at its core. The approach takes advantage of our recent work demonstrating that X-ray computed tomography (XCT) can identify microstructures within inhalation powders. In this project we will address key technological challenges in sample analysis and image analysis to develop quantitative metrics of powder microstructures. These challenges will include understanding how much of the dosage form needs to be analysed to obtain a statistically relevant assessment of individual dose units; what the limit of detection is for the techniques in terms of the concentrations of drug within the formulations; how sensitive the technique is to changes in chemical composition, as well as understanding the sources of variability between measurements to assess the translatability of the technique.