Impact of Surfactants on the Performance of Clopidogrel-Copovidone Amorphous Solid Dispersions: Increased Drug Loading and Stabilization of Nanodroplets,Pharmaceutical Research

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Impact of Surfactants on the Performance of Clopidogrel-Copovidone Amorphous Solid Dispersions: Increased Drug Loading and Stabilization of Nanodroplets
Pharmaceutical Research ( IF 3.5 ) Pub Date : 2022-01-10 , DOI: 10.1007/s11095-021-03159-w
Clara E Correa Soto ₁ , Yi Gao ₂ , Anura S Indulkar ₃ , Keisuke Ueda ₄ , Geoff G Z Zhang ₃ , Lynne S Taylor ₁

Affiliation

Purpose

Surfactants are increasingly being added to amorphous solid dispersion (ASDs) formulations to enhance processability and release performance. The goal of the current work was to investigate the impact of cationic, anionic and non-ionic surfactants on the rate and extent of clopidogrel (CPD) release from copovidone-based ASDs.

Methods

CPD release was evaluated for ASDs with different drug loadings using a surface normalized intrinsic dissolution apparatus. Studies were also carried out using dynamic light scattering, zeta potential measurements, and nuclear magnetic resonance spectroscopy to probe the impact of surfactants on drug-rich nanodroplet physical stability and clopidogrel-surfactant interactions.

Results

CPD ASDs showed good release for drug loadings as high as 40%, before the release fell off a cliff at higher drug loadings. Only sodium dodecyl sulfate, added at a 5% level, was able to improve the release at 50% drug loading, with other surfactants proving to be ineffective. However, some of the surfactants evaluated did show some benefits in improving nanodroplet stability against size enlargement. Ionic and non-ionic surfactants were observed to interact differently with CPD-rich nanodroplets, and variations in the kinetics and morphology of water-induced phase separation were noted in the presence and absence of surfactants in ASD films.

Conclusions

In summary, addition of surfactants to ASD formulations may lead to some improvements in formulation performance, but predictive capabilities and mechanisms of surfactant effect still require further studies.

Graphical abstract

中文翻译：

表面活性剂对氯吡格雷-共聚维酮无定形固体分散体性能的影响：增加载药量和纳米液滴的稳定性

目的

表面活性剂越来越多地被添加到无定形固体分散体 (ASD) 配方中，以提高加工性能和释放性能。当前工作的目标是研究阳离子、阴离子和非离子表面活性剂对共聚维酮 ASD 释放氯吡格雷 (CPD) 的速率和程度的影响。

方法

使用表面归一化固有溶出度仪评估具有不同载药量的 ASD 的 CPD 释放。还使用动态光散射、zeta 电位测量和核磁共振光谱进行了研究，以探测表面活性剂对富含药物的纳米液滴物理稳定性和氯吡格雷-表面活性剂相互作用的影响。

结果

CPD ASD 在载药量高达 40% 的情况下表现出良好的释放，然后在更高的载药量下释放掉下悬崖。只有添加 5% 水平的十二烷基硫酸钠能够改善 50% 载药量时的释放，而其他表面活性剂被证明是无效的。然而，评估的一些表面活性剂确实显示出在提高纳米液滴稳定性以防止尺寸增大方面的一些好处。观察到离子和非离子表面活性剂与富含 CPD 的纳米液滴的相互作用不同，并且在 ASD 膜中存在和不存在表面活性剂的情况下，注意到水诱导相分离的动力学和形态的变化。