title: A uHPLC-MS mathematical modeling approach to dry powder inhaler single agglomerate analysis.
abstract: Demonstration of content uniformity (CU) is critical toward the successful development of dry powder inhalers (DPIs). Methods for unit dose CU determination for DPI products are well-established within the field of respiratory science. Recent advances in the area include a uHPLC-MS method for high-throughput uniformity analysis, which allows for a greater understanding of blending operations as the industry transitions to a quality-by-design approach to development. Further enhancements to this uHPLC-MS method now enable it to determine CU and sample weight at the single agglomerate level, which is roughly 50× smaller than a unit dose. When coupled with optical microscopy-based agglomerate sizing, the enhanced uHPLC-MS method can also predict the density and porosity of individual agglomerates. Expanding analytical capabilities to the single agglomerate level provides greater insights and confidence in the DPI manufacturing process.
authors.affiliation: Merck Sharp & Dohme Corp, Summit, NJ, USA. Justin.pennington@merck.com
authors.forename: Justin
authors.initials: J
authors.lastname: Pennington
authors.forename: John
authors.initials: J
authors.lastname: Lena
authors.forename: Joseph
authors.initials: J
authors.lastname: Medendorp
authors.forename: Gary
authors.initials: G
authors.lastname: Ewing
mesh_terms: D000280:Administration, Inhalation; D002851:Chromatography, High Pressure Liquid; D058995:Dry Powder Inhalers / Q000295:instrumentation*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008433:Mathematics; D008962:Models, Theoretical; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D011208:Powders