激光衍射测定PMDI粒径外文).pdfVIP

Respiratory Drug Delivery 2014 – Cooper et al. A QbD Method Development Approach for the Ex-actuator Particle Size Distribution (PSD) Determination of pMDIs by Laser Diffraction 1 1 Andy Cooper, Chris Blatchford, and Stephen Stein2 1 3M Drug Delivery Systems Ltd, Loughborough, Leicestershire,UK 23M Drug Delivery Systems, St. Paul, MN, USA KEYWORDS: pressurized metered dose inhaler (pMDI), quality by design (QbD), laser diffraction, method development, particle size IntRODuCtIOn The aerodynamic particle size distribution (APSD) is a critical quality attribute (CQA) of orally inhaled and nasal drug products (OINDPs). Cascade impactor methodology [1] is typically used to determine this during development and registered product testing. However, this is a time consuming analysis which makes it impractical as a rapid screening tool for early phase develop- ment and investigations. Laser diffraction (LD) analysis of the ex-actuator plume has previously been proposed as an alternative [2] for geometric particle size distribution (PSD) determination. This is considered appropriate as the measured ex-actuator PSD would be influenced by the active pharmaceutical ingredient (API) within the formulation in three ways. One, the dry API par- ticles would be present in the actuation plume after atomization. Two, droplet formation during atomization may be influenced by the particle size of the API [3]. Lastly, the API concentration will influence the number