Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
AstraZeneca R&D, Pepparedsleden 1, 43150 Mölndal, Sweden.
Int J Pharm. 2016 Dec 5;514(2):341-352. doi: 10.1016/j.ijpharm.2016.03.038. Epub 2016 Mar 24.
In this study, we investigated the influence of deformability of specifically-engineered guest particles on the tensile strength of tablets of interactive mixtures. The binder polyvinylpyrrolidone (PVP) of different molecular weights were spray dried with l-leucine to create guest particle formulations. The guest particle formulations were characterized by their particle size, surface l-leucine concentration and glass transition temperature (Tg). These spray-dried particles were then blended with paracetamol to form interactive mixtures, which were compacted into tablets and tablet tensile strength and elastic recovery were determined. The guest particles had particle diameters in the range of 1-10μm, and surfaces that were l-leucine enriched. The Tg of guest particle formulations increased with increasing molecular weight of the PVP. All the guest particle formulations formed an observed homogeneous interactive mixture with paracetamol. The tensile strength of the tablets of interactive mixtures increased with decreasing Tg of the guest particles. In these interactive mixtures, higher tensile strength was also associated with lower tablet elastic recovery. The elastic recovery of the tablets showed a correlation with the elastic recovery of the tablets of guest particles. Thus, our results indicated that the deformability of guest particles dictates the tensile strength of the tablets of these interactive mixtures.
在这项研究中,我们研究了经过特殊设计的客体粒子的变形性对交互式混合物片剂拉伸强度的影响。不同分子量的聚乙烯吡咯烷酮 (PVP) 与亮氨酸一起喷雾干燥,制成客体粒子配方。客体粒子配方的特征在于其粒径、表面亮氨酸浓度和玻璃化转变温度 (Tg)。然后,将这些喷雾干燥的颗粒与对乙酰氨基酚混合形成交互式混合物,将其压制成片剂,并测定片剂的拉伸强度和弹性恢复。客体颗粒的粒径在 1-10μm 范围内,表面富含亮氨酸。客体粒子配方的 Tg 随 PVP 分子量的增加而增加。所有的客体粒子配方都与对乙酰氨基酚形成了可观察到的均匀交互式混合物。交互式混合物片剂的拉伸强度随客体粒子 Tg 的降低而增加。在这些交互式混合物中,较高的拉伸强度也与较低的片剂弹性恢复有关。片剂的弹性恢复与客体粒子片剂的弹性恢复呈相关关系。因此,我们的结果表明,客体粒子的变形性决定了这些交互式混合物片剂的拉伸强度。