Eudragit® RL as a stabilizer for supersaturation and a substrate for nanocrystal formation

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Abstract

In order to optimize supersaturation levels and avoid early drug precipitation, Eudragit® RL was tested as a carrier in solid dispersions, either alone or in combination with a hydrophilic polymer (PVP K25). In vitro dissolution performance of the spray dried solid dispersions was tested. The phase behavior of the produced solid dispersions was analyzed as well as dissolution precipitates. In case of weak acid model compounds (indomethacin and naproxen), the incorporation of Eudragit® RL resulted in a prolongation of supersaturation. A combination of PVP and Eudragit® RL led to high and stable drug concentrations. Eudragit® RL was only suited as a carrier in combination with higher drug loadings. Phase behavior analysis of the produced solid dispersions showed that Eudragit® RL could form glass solutions, and precipitate analysis showed that these drug-polymer combinations remained amorphous after in vitro dissolution for 24 h. Surprisingly, indomethacin and naproxen also formed nanocrystals in presence of Eudragit® RL. These nanocrystals were formed by a dynamic interplay of dissolution, sorption and desorption. A charge interaction between anionic drugs and a cationic polymer provided a high driving force for sorption, which was necessary for nanocrystal formation and supersaturation stabilization.

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