Coarse Lactose Particles as Dispersion Enhancers During Aerosolization of Dry Powder Formulations

Edward Yost, Vibha Puri, and Ajit Narang

Small Molecule Pharmaceutical Sciences, Genentech, Inc., One DNA Way, South San Francisco, CA, 94080, USA

Summary

A combination of coarse and fine particle size grade excipients is typically used in dry powder inhaler (DPI) formulations to improve the uniformity of drug distribution.  In this study, the role of coarse particles as dispersing agents of fine particle agglomerates during powder dispersion was investigated by dry dispersion laser diffraction analysis (LDA).  LDA allowed fast and effective investigation of fine particle interactions typical in DPI drug products.  Particles with different cohesivity (lactose monohydrate versus soda-lime glass) and morphology were compared with respect to their effectiveness in deagglomerating fine particle agglomerates.  The forces controlling these interactions – cohesive forces between particles and dispersion forces acting upon agglomerates – were used to describe the relationship observed between the concentration of added coarse particles and the proportion of fine mass fraction (FMF, defined as particles <6 µm by LDA).  In addition, the effect of particle density on FMF was investigated using denser coarse particles.  Understanding the balance of these forces allows rational selection of excipients to use in a DPI drug product.