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 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 0.001mm2 and above within a 11.2mm×9.0mm field of view. It was found that blends prepared with larger API particles (60–200 mesh) contain agglomerated API domains ≥0.1mm2. 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.

这份研究报告描述了一项粉末混合模拟研究，该研究使用20毫升闪烁瓶和台式旋转混合器，对每个样品以2克的规模进行。为了研究平均粒径和粒径分布对一种活性药物成分（API）混合行为的影响，使用60目、80目、100目、200目和325目的美国标准筛将原料药分成筛分级分。每个级分都与两种辅料（羟丙基甲基纤维素和微晶纤维素）混合长达20分钟。然后通过近红外化学成像（NIR - CI）系统对混合样品进行分析。NIR - CI系统能够在11.2毫米×9.0毫米的视野内测量0.001平方毫米及以上的API颗粒/区域（团聚体）。研究发现，由较大API颗粒（60 - 200目）制备的混合物含有≥0.1平方毫米的团聚API区域。由较细API颗粒（≤325目）制备的混合物呈现出随机混合的特征。这种简单有效的方法可用于制剂开发中API混合行为的评估。