Micronization of N-acetylcysteine by supercritical fluid: Evaluation of in vitro and in vivo biological activity

- The micronization process provided greater solubility of NAC.
- The micronization process increased the antioxidant activity.
- By PXRD it has been shown that micronized NAC exhibits different crystalline structure of the raw compound.
- NAC presented biological activity even in a micronized concentration 100 times lower than non-micronized NAC.
- The compound is free of residual solvent, being safe for human consumption.

The micronization techniques by supercritical fluid have been gaining more prominence especially in the pharmaceutical area. N-acetylcysteine (NAC) is a mucolytic which has emerged as a promising molecule for the treatment of neuropsychiatric disorders. This work aims to study the micronization process of NAC by the anti-solvent SEDS technique, and to evaluate both in vitro and in vivo improvements in the properties of this compound. Herein we demonstrate that the micronization process led to a 245-fold reduction in particle size. In vitro tests showed an increase in dissolution rate, in antioxidant activity and beyond modification of the crystalline structure. In the in vivo tests, it was observed that the micronization process decreased the minimum effective concentration of NAC that induced anxiolytic-like effects in zebrafish. Micronization may thus increase bioavailability and potentiate the therapeutic effect of drugs, opening new horizons in the area of supercritical fluid micronization in the pharmaceutical industry.

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