Development and Optimisation of a Particle Sizing Methodology for Early Screening of DPI Carrier Based Formulations using Laser Diffraction.
James McNeill1, Jim Clay1, Olivia Brittain1
1Kindeva Drug Delivery Ltd Loughborough, Leicestershire, LE11 5RB, UK
Summary
Aerodynamic Particle Size Distribution (APSD) is recognised as a Critical Quality Attribute (CQA) in the in vitro characterisation of Orally Inhaled and Nasal Drug Products (OINDPs). The established instrumentation for measuring APSD of inhaled products is the multistage cascade impactor (CI). Use of laser diffraction for Particle Size Distribution (PSD) measurement offers an efficient and simplified alternative approach for early screening of Dry Powder Inhaler (DPI) formulations; however, the lack of component specificity may be a drawback. It is therefore essential to have a suitable separation strategy. In this study, a Next Generation Impactor (NGI), DPI preseparator and throat were interfaced with a Sympatec HELOS with INHALER adapter. This test configuration enabled a comparison of mean diameter (D50) from laser diffraction PSD data against mass median aerodynamic diameter (MMAD) data generated by NGI. The correlation between D50 and MMAD was improved when the standard DPI preseparator insert was coated with 1% w/v Brij® 35 in 20/80 %v/v ethanol/glycerol solution, and then further enhanced by replacing the standard insert with a 30 L/min, 5 µm cut-off insert. Further development showed that using two stacked preseparators in series, each containing a coated 30 L/min, 5 µm cut-off insert, generated the closest correlation between D50 and MMAD. This novel methodology could enable efficient early screening of formulations in DPI product development.