Revealing the mechanism of morphological variation of amorphous drug nanoparticles formed by aqueous dispersion of ternary solid dispersion
Revealing the mechanism of morphological variation of amorphous drug nanoparticles formed by aqueous dispersion of ternary solid dispersion
复制标题
揭示三元固体分散体水分散体形成的非晶态药物纳米粒形貌变化机制
DOI：
10.1016/j.ijpharm.2021.120984
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发表时间：
2021
影响因子：
5.8
通讯作者：
Moribe Kunikazu
中科院分区：
文献类型：
--
作者：
Zhao Zhijing;Higashi Kenjirou;Ueda Keisuke;Moribe Kunikazu
制备了不同质量比的普罗布考（PBC）/羟丙甲纤维素（HPMC）/十二烷基硫酸钠（SDS）三元固体分散体（SDs），考察了HPMC和SDS对PBC无定形纳米粒形成的影响。采用动态光散射和低温透射电子显微镜（cryo-TEM）研究了不同组成的SDs制备的PBC纳米粒子的形貌变化。PBC纳米颗粒的粒度与圆度的统计分析是基于低温TEM图像进行的。观察到PBC纳米颗粒的形态与HPMC和SDS的量之间存在明显的相关性，无论是在SD中混合还是在水溶液中预溶解。在SD中混合的HPMC被证明在确定离散的无定形PBC纳米颗粒的初级粒径中起主要作用。基于13 C固体核磁共振谱，这一现象应是由于增加的尺寸的富含PBC的域的SD，这取决于混合的HPMC的量减少。虽然HPMC的预溶部分对一次粒径的影响较小，但发现它抑制了无定形PBC纳米颗粒的颗粒团聚和重结晶。另一方面，在SDS中混合足够的SDS可以抑制在水分散后的水浸渍和纳米颗粒演变（团聚和结晶）过程中的PBC丰富的域的尺寸增强。预溶解的SDS可以抑制PBC纳米粒子的团聚，最终形成数百个不规则的纳米级结构。由于在水浸过程中尺寸增加，它们的尺寸仍然略大于高比例混合SDS获得的尺寸。本研究的结果阐明了向SD中添加聚合物和表面活性剂以制备药物纳米颗粒制剂的有用性和必要性。
Probucol (PBC)/hypromellose (HPMC)/sodium dodecyl sulfate (SDS) ternary solid dispersions (SDs) of various weight ratios were prepared and evaluated to unveil the effect of HPMC and SDS on the formation of amorphous PBC nanoparticles. The morphological variation of the PBC nanoparticles prepared using SDs of different compositions was determined using dynamic light scattering and cryogenic transmission electron microscopy (cryo-TEM). Statistical analysis of particle size versus roundness of PBC nanoparticles was carried out based on cryo-TEM images. A clear correlation was observed between the morphologies of the PBC nanoparticles and the amounts of HPMC and SDS, either admixed in SDs or pre-dissolved in an aqueous solution. The admixed HPMC in SDs was demonstrated to play the major role in determining the primary particle sizes of discrete amorphous PBC nanoparticles. Based on13C solid-state NMR spectroscopy, this phenomenon should be due to the enlarged size of the PBC-rich domains in SDs, which depended on the decreasing amounts of admixed HPMC. Although the pre-dissolved part of HPMC had less impact on the primary particle sizes, it was found to inhibit the particle agglomeration and recrystallization of amorphous PBC nanoparticles. On the other hand, sufficient SDS admixed in SDs could suppress the size enhancement of the PBC-rich domains during water immersion and nanoparticle evolution (agglomeration and crystallization) after aqueous dispersion. The pre-dissolved SDS could restrain the agglomeration of amorphous PBC nanoparticles, ultimately forming hundreds of irregular nanometer-order structures. Since the increase in size during water immersion, their sizes were still slightly larger than those obtained with a high portion of admixed SDS. The findings of this study clarified the usefulness and necessity of adding polymers and surfactants to SDs to fabricate drug nanoparticle formulations.