Mangal Sharad, Gengenbach Thomas, Millington-Smith Doug, Armstrong Brian, Morton David A V, Larson Ian
Drug Delivery, Disposition and Dynamics, Monash University, Royal Parade, Parkville, VIC 3052, Australia.
CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, VIC 3168, Australia.
Eur J Pharm Biopharm. 2016 May;102:168-77. doi: 10.1016/j.ejpb.2016.03.012. Epub 2016 Mar 10.
In this study, we aimed to investigate the effects cohesion of small surface-engineered guest binder particles on the flow behaviour of interactive mixtures. Polyvinylpyrrolidone (PVP) - a model pharmaceutical binder - was spray-dried with varying l-leucine feed concentrations to create small surface-engineered binder particles with varying cohesion. These spray-dried formulations were characterised by their particle size distribution, morphology and cohesion. Interactive mixtures were produced by blending these spray-dried formulations with paracetamol. The resultant blends were visualised under scanning electron microscope to confirm formation of interactive mixtures. Surface coverage of paracetamol by guest particles as well as the flow behaviour of these mixtures were examined. The flow performance of interactive mixtures was evaluated using measurements of conditioned bulk density, basic flowability energy, aeration energy and compressibility. With higher feed l-leucine concentrations, the surface roughness of small binder particles increased, while their cohesion decreased. Visual inspection of the SEM images of the blends indicated that the guest particles adhered to the surface of paracetamol resulting in effective formation of interactive mixtures. These images also showed that the low-cohesion guest particles were better de-agglomerated that consequently formed a more homogeneous interactive mixture with paracetamol compared with high-cohesion formulations. The flow performance of interactive mixtures changed as a function of the cohesion of the guest particles. Interactive mixtures with low-cohesion guest binder particles showed notably improved bulk flow performance compared with those containing high-cohesion guest binder particles. Thus, our study suggests that the cohesion of guest particles dictates the flow performance of interactive mixtures.
在本研究中,我们旨在探究小尺寸表面工程化客体黏合剂颗粒的内聚力对交互式混合物流动行为的影响。将聚乙烯吡咯烷酮(PVP)——一种典型的药用黏合剂——与不同的L-亮氨酸进料浓度进行喷雾干燥,以制备具有不同内聚力的小尺寸表面工程化黏合剂颗粒。这些喷雾干燥制剂通过其粒度分布、形态和内聚力进行表征。通过将这些喷雾干燥制剂与对乙酰氨基酚混合来制备交互式混合物。在扫描电子显微镜下观察所得混合物,以确认交互式混合物的形成。检测了客体颗粒对乙酰氨基酚的表面覆盖率以及这些混合物的流动行为。使用条件堆积密度、基本流动性能量、通气能量和可压缩性的测量值来评估交互式混合物的流动性能。随着L-亮氨酸进料浓度的增加,小黏合剂颗粒的表面粗糙度增加,而其内聚力降低。对混合物的扫描电子显微镜图像进行目视检查表明,客体颗粒附着在对乙酰氨基酚表面,从而有效地形成了交互式混合物。这些图像还表明,与高内聚力制剂相比,低内聚力客体颗粒的解聚效果更好,因此与对乙酰氨基酚形成了更均匀的交互式混合物。交互式混合物的流动性能随客体颗粒的内聚力而变化。与含有高内聚力客体黏合剂颗粒的混合物相比,含有低内聚力客体黏合剂颗粒的交互式混合物表现出显著改善的整体流动性能。因此,我们的研究表明,客体颗粒的内聚力决定了交互式混合物的流动性能。