Drug Product Development, Research and Development, AbbVie Inc., N Waukegan Road, North Chicago, IL, 60064, USA.
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN, 47907, USA.
Pharm Res. 2022 Feb;39(2):381-397. doi: 10.1007/s11095-022-03183-4. Epub 2022 Feb 15.
To understand the role of different surfactants, incorporated into amorphous solid dispersions (ASDs) of ritonavir and copovidone, in terms of their impact on release, phase behavior and stabilization of amorphous precipitates formed following drug release.
Ternary ASDs with ritonavir, copovidone and surfactants (30:70:5 w/w/w) were prepared by rotary evaporation. ASD release performance was tested using Wood's intrinsic dissolution rate apparatus and compared to the binary drug-polymer ASD with 30% drug loading. Size measurement of amorphous droplets was performed using dynamic light scattering. Solid state characterization was performed using attenuated total reflectance-infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy.
All surfactant-containing ASDs showed improvement over the binary ASD. Span 85 and D-α-tocopheryl polyethylene glycol succinate (TPGS) showed complete release with no evidence of AAPS or crystallization whereas Span 20 and Tween 80 showed < 50% release with amorphous amorphous phase separation (AAPS). Span 20 also induced solution crystallization. Sodium dodecyl sulfate (SDS) showed very rapid, albeit incomplete (~ 80%) release. AAPS was not observed with SDS. However, crystallization on the dissolving solid surface was noted. Span 20 and TPGS formed the smallest and most size-stable droplets with ~ 1 µm size whereas coalescence was noted with other surfactants.
Surfactants improved the release performance relative to the binary ASD. Different surfactant types impacted overall performance to varying extents and affected different attributes. Overall, Span 85 showed best performance (complete release, no crystallization/AAPS and small droplet size). Correlation between physicochemical properties and surfactant performance was not observed.
了解不同表面活性剂在胶态分散体（ASD）中的作用，以及它们对药物释放后形成的无定形沉淀的释放、相行为和稳定化的影响。
通过旋转蒸发法制备了含有利托那韦、共聚维酮和表面活性剂（30:70:5 w/w/w）的三元 ASD。使用 Wood 固有溶解速率仪测试了 ASD 的释放性能，并与 30%载药量的二元药物-聚合物 ASD 进行了比较。使用动态光散射法测量了无定形液滴的尺寸。采用衰减全反射-红外光谱、差示扫描量热法和扫描电子显微镜对固体状态进行了表征。
所有含表面活性剂的 ASD 均优于二元 ASD。Span 85 和 D-α-生育酚聚乙二醇琥珀酸酯（TPGS）表现出完全释放，没有无定形聚集物（AAPS）或结晶的迹象，而 Span 20 和吐温 80 则显示出 < 50%的释放，存在无定形-无定形相分离（AAPS）。Span 20 还诱导溶液结晶。十二烷基硫酸钠（SDS）表现出非常快速的释放，尽管不完全（约 80%）。SDS 未观察到 AAPS。然而，在溶解固体表面上观察到结晶。Span 20 和 TPGS 形成的液滴最小且最稳定，粒径约为 1 µm，而其他表面活性剂则发生了聚结。
与二元 ASD 相比，表面活性剂改善了释放性能。不同类型的表面活性剂对整体性能的影响程度不同，影响了不同的属性。总体而言，Span 85 表现出最佳性能（完全释放、无结晶/AAPS 和小液滴尺寸）。未观察到物理化学性质与表面活性剂性能之间的相关性。
