Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia.
Catalent Pharma Solutions, Catalent Germany Schorndorf GmbH, Steinbeisstraße 1-2, 73614, Schorndorf, Germany.
AAPS PharmSciTech. 2021 Dec 10;23(1):17. doi: 10.1208/s12249-021-02150-3.
We report here on improved uniformity of blends of micronised active pharmaceutical ingredients (APIs) using addition of spherical agglomerates of lactose and enhanced blend flow to improve tablet content uniformity with higher API loads. Micromeritic properties and intra-particle porosity (using nano-computed X-ray tomography) of recently introduced spherical agglomerates of lactose and two standard lactose grades for the direct compression processes were compared. Powder blends of the individual lactose types and different micronised API drug loads were prepared and subjected to specific conditions that can induce API segregation. Tablet content uniformity during direct compression was related to the lactose material attributes. The distinctive micromeritic properties of the lactose types showed that spherical agglomerates of lactose had high intra-particle porosity and increased specific surface area. The stability of binary blends after intense sieving was governed by the intra-particle porosity and surface roughness of the lactose particles, which determined the retention of the model substance. Greater intra-particle porosity, powder specific surface area, and particle size of the spherical agglomerates provided greater adhesion of micronised particles, compared to granulated and spray-dried lactose. Thus the spherical agglomerates provided enhanced final blend flow and uniformity of tablet content at higher drug loads.
我们在此报告了使用添加乳糖球型团聚物和增强混合流动性来提高片剂含量均匀度和更高 API 负载的方法，从而改善了微粉化活性药物成分 (API) 混合物的均匀性。比较了最近推出的用于直接压片工艺的乳糖球型团聚物和两种标准乳糖等级的微粉化 API 的颗粒特性和颗粒内孔隙率（使用纳米计算 X 射线断层摄影术）。制备了各个乳糖类型的粉末混合物和不同的微粉化 API 药物负载，并对其进行了可能导致 API 分离的特定条件的处理。直接压片过程中的片剂含量均匀度与乳糖材料特性有关。乳糖类型的独特颗粒特性表明，乳糖球型团聚物具有高颗粒内孔隙率和增加的比表面积。经过强烈筛分后二元混合物的稳定性取决于乳糖颗粒的颗粒内孔隙率和表面粗糙度，这决定了模型物质的保留。与颗粒状和喷雾干燥乳糖相比，球形团聚物的更大颗粒内孔隙率、粉末比表面积和颗粒尺寸提供了更大的微粉颗粒附着力。因此，球形团聚物在更高的药物负载下提供了增强的最终混合流动性和片剂含量均匀性。
