title: Measurement of drug agglomerates in powder blending simulation samples by near infrared chemical imaging.
abstract: This research note describes a powder blending simulation study conducted using 20-mL scintillation vials and a bench-top rotating mixer on a scale of 2g for each sample. In order to investigate the impact of mean particle size and size distribution on blending behavior of an active pharmaceutical ingredient (API), the drug substance was separated into sieve fractions using the US standard sieves of 60, 80, 100, 200, and 325mesh. Each of the fractions was mixed with two excipients (hydroxypropyl methylcellulose and microcrystalline cellulose) for up to 20min. Then the blending samples were analyzed by a near infrared chemical imaging (NIR-CI) system. The NIR-CI system was able to measure API particles/domains (agglomerates) at 0.001mm(2) and above within a 11.2mmx9.0mm field of view. It was found that blends prepared with larger API particles (60-200 mesh) contain agglomerated API domains > or =0.1mm(2). The blends prepared with finer API particles (< or =325 mesh) show the characteristics of a randomized mixing. This simple and effective method can be used for evaluation of blending behavior for APIs in formulation development.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, PA 19477, USA. wli1@prdus.jnj.com
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.forename: Abraham
authors.initials: A
authors.lastname: Woldu
authors.forename: Richard
authors.initials: R
authors.lastname: Kelly
authors.forename: Jim
authors.initials: J
authors.lastname: McCool
authors.forename: Rick
authors.initials: R
authors.lastname: Bruce
authors.forename: Henrik
authors.initials: H
authors.lastname: Rasmussen
authors.forename: John
authors.initials: J
authors.lastname: Cunningham
authors.forename: Denita
authors.initials: D
authors.lastname: Winstead
mesh_terms: D010316:Particle Size; D011208:Powders; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013678:Technology, Pharmaceutical
chemical_list: D011208:Powders