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

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.