Development of amorphous solid dispersions of cannabidiol: Influence of the carrier, the hot-melt extrusion parameters and the use of a crystallization inhibitor

Abstract

Hot-melt extrusion has been widely used to manufacture amorphous solid dispersion to enhance water solubility of molecules. In this study, the influence of the polymer, the extrusion parameters and the use of a crystallization inhibitor were investigated for the production of amorphous solid dispersions.Three polymers, namely Kollidon® VA 64, Parteck® MXP and Eudragit® EPO, were first investigated to manufacture amorphous solid dispersions with cannabidiol as a model poor water-soluble drug. Selected mixtures were extruded at three temperatures and two screw speeds. Eudragit® NM 30D, was added to the formulation which had the most appropriated dissolution behavior in order to highlight the prevention of the recrystallization.Dissolution tests first showed a difference between polymers regarding the dissolution of cannabidiol. Eudragit® EPO allowed the highest and the quickest dissolution of CBD (80% after 30 min), so it was selected for the rest of the study. The dissolution tests on the ASD produced with different extrusion parameters showed that the temperature had an influence on the cannabidiol concentration upkeep during the test.Finally, it was observed that Eudragit® NM 30D was able to maintain the elevated CBD concentration during at least 4 h, while the same formulation without this inhibitor was subjected to a drop of cannabidiol concentration.This study showed the importance of first, the choice of polymers for the manufacture of amorphous solid dispersions containing cannabidiol. Secondly, the influence of the extrusion temperature on the upkeep of the cannabidiol concentration was highlighted. Finally, it was shown that the use of a crystallization inhibitor prevents the cannabidiol recrystallization during at least 4 h of dissolution.