Effect of Air Jet Micronization on Particle Properties and the Correlation of Interparticle Interactions by Atomic Force Microscopy with Surface Forces by Inverse Gas Chromatography
Vibha Puri,1 Jagdeep Shur2, Robert Price2, Andreas Stumpf1, & Ajit Narang1
1Small Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
2Nanopharm Ltd., Cavendish House, Newport NP10 8FY, UK
Micronization of pharmaceutical powders can induce structural and surface disorder on the surface of constituent particles, which can impact their aerodynamic performance in dry powder inhaler (DPI) formulations. Furthermore, these materials undergo surface re-construction on storage, which can then impact their physicochemical properties over time. Identifying and mapping the interparticle interactions that can be directly linked to aerodynamic performance is challenging. In this work, we studied the correlation of interparticle interactions measured by atomic force microscopy (AFM) with particle surface forces by inverse gas chromatography (IGC) for a model active pharmaceutical ingredient (API), Compound A.
Micronized API produced by air jet milling was stored under different stress conditions. The drug-drug cohesive interactions and drug-lactose adhesive interactions were measured by AFM. The cohesive-adhesive balance (CAB) ratio was calculated. The freshly micronized API showed an AFM CAB ratio of 0.69 that suggested greater API-lactose adhesive interactions, while its IGC CAB ratio of 1.16 suggested higher API-API cohesive interactions. Nonetheless, both techniques reported reducing CAB ratio upon storage of the micronized API at accelerated conditions of temperature and humidity, suggesting increase in API-lactose adhesive interactions and lowering of API cohesive interactions. The magnitude of change in AFM CAB ratios was greater than the IGC CAB ratios, indicating greater sensitivity of AFM technique. In summary, while the initial CAB may depend on the technique used for measurement, changes in the CAB on storage were consistent across the two analytical tools investigated.