Measurement of drug agglomerates in powder blending simulation samples by near infrared chemical imaging

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 2 g 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 325 mesh. Each of the fractions was mixed with two excipients (hydroxypropyl methylcellulose and microcrystalline cellulose) for up to 20 min. 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 0.001 mm2 and above within a 11.2 mm × 9.0 mm field of view. It was found that blends prepared with larger API particles (60–200 mesh) contain agglomerated API domains ≥0.1 mm2. The blends prepared with finer API particles (≤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.