Investigation and Resolution of Particle Re-entrainment in NGI Analysis of a Spray Dried Formulation Emitted from a Dry Powder Inhaler
Eric Peterson1, Cameron Kadleck1, Jordan Oliver1, Adam Schneiderhan1, Maureen Kadleck1, Karina Joyce2, Max Allsworth2, Jacob Harker3
1Lonza AG, 63045 Corporate Place, Bend, Oregon 97701, United States of America
2Owlstone Medical, 183 Cambridge Science Park, Milton Rd, Cambridge CB4 0GJ, UK
3BnL Pharma Solutions, 15 Davies Meadow, Wantage, Oxon, OX12 0GG, UK
Summary
Aerodynamic Particle Size Distribution (APSD) is a key metric for pharmaceutical products intended for inhalation delivery, primarily determined using multistage cascade impactors like the Next Generation Pharmaceutical Impactor (NGI). Particle re-entrainment can severely affect measurement of the aerosol size profile, inhibiting design and engineering of respirable particles. In this study, several industry-standard pan coating solutions displayed high degrees of re-entrainment during NGI testing of a spray-dried intermediate (SDI) designed as a lung cancer diagnostic. Instead of allowing the coating solution to dry before testing, loading the pans with an aqueous solution was found to greatly reduce re-entrainment, enabling more accurate APSD determination. In our study, the commercially available high resistance RS01 Dry Powder Inhaler (DPI) was used to aerosolize a powder engineered to have an almost entirely respirable aerodynamic particle size distribution. The liquid loading method performed well with 10 or 40mg capsule fill-weights, while more typical impactor adhesive coatings gave significantly different results, which were also dependent on capsule fill-weight.