Micronização de n-acetilcisteína e trans-resveratrol pela técnica SEDS e avaliação das atividades biológicas in vitro e in vivo

Trans-resveratrol compounds and N-acetylcysteine are potent antioxidants of great industrial interest. The trans-resveratrol is a polyphenol found in various foods, especially in Blueberry, grape seeds, in the skin of the grapes and in red wine. This compound offers numerous health benefits, such as: antioxidant, antifungal, antiinflammatory, antiplatelet, cardioprotective among others. NAcetylcysteine is a thiol (-SH) with a potent antioxidant effect. This compound comes demonstrating preventive effect as protector in chronic kidney disease, cancer, pulmonary insufficiency among others. The technique Solution Enhanced Dispersion by Supercritical Fluids (SEDS), is a method that can be applied to micronization compounds with bioactive properties. In this context, the objective of this work was to evaluate the use of the method in the micronization of SEDS transresveratrol and N-acetylcysteine using both a DCC 2 with 3 central points, evaluating the influence of the concentration of the compound (4, 12, and 20 mg∙mL), temperature (308, 313 and 318 F) and pressure (80, 100 and 120 bar) operating in relation to average particle diameter (Dp). In addition to evaluating biological properties in vitro and in vivo.The average size of the drug before processing of the transresveratrol was 36.65 μm and the NAC of 709.82 μm and the best result of both compounds were obtained in the same conditions: concentration of 20 mg∙mL, 80 bar pressure and a temperature of 308 F, which reduced the original size at about 166.59 times getting an average diameter of 0.22 μm particles for trans-resveratrol and reduction of about 248.19 times getting Dp of 2.86 μm for N-acetylcysteine. In relation to the properties of Trans-resveratrol after the micronization process, the solubility of the compound increased in water, about 2.8 times compared to the non-micronized compound, increasing the dissolution rate by 1.8 times and increasing the activity Antioxidant of the compound. From DSC and PXRD analyzes, we observed that there were modifications in the trans-resveratrol crystal structure. The physicochemical properties of the micronized versus non-micronized NAC observed an increase in the dissolution rate, and only the contact of the solvent with the compound occurs totally dissolution of the same, besides the increase of the antioxidant activity. From the PXRD analysis it was found that micronized NAC reduced crystallinity after the process, and by DSC analysis it was found that there was a shift of the compound melting point indicative of structure modifications. It was proved by the FTIR found that there was no degradation of the compounds. Finally, the residual solvent analysis using GC-MS and GC-FID, it was proven that the micronized compounds are in accordance with the standards for human consumption. Thus, the fact that the best results have been obtained in milder conditions of temperature and pressure is relevant, as well as reducing the cost of the process there is the possibility of working with heat-sensitive compounds. Finally, in the in vivo tests in Zebrafish it was observed that the micronized NAC decreased the minimum effective concentration in 100 times, obtaining even anxiolytic type effect of the non-micronized compound. Therefore, micronization increased the bioavailability and potentiated the therapeutic effects, in vitro and in vivo, of the drugs, which opens new horizons in the area of supercritical fluid micronization for both the pharmaceutical, chemical and food industries.