Emulsão água-em-água como uma diferente abordagem para produção micropartículas à base de xilana contendo mesalazina

Abstract

The water-in-water emulsion technique could be used to produce microparticles without using harmful solvents. However, there are few reports in the literature showing the encapsulation of low molecular weight drugs in microparticles using such technique. Therefore, the aim of this work was to develop ways to entrap drugs with low molecular weight by means of the water-in-water emulsion technique using mesalazine as a model drug. An approach using double crosslinking, with CaCl2, has been proposed to promote higher encapsulation rates. For the production and choice of the best microparticle formulation, a complete factorial design 23 and a phase diagram were performed, respectively. The morphology of the particles and their mean diameter size were evaluated by optical microscopy with a 10x amplitude. 500 particles were counted in triplicate. For a better understanding of the chemical characteristics and interactions among the drug, the crosslinkers and the polymer, infrared and X-ray diffractometry (XRD) analyzes were carried out. In addition, the drug's release profile was assessed using spectrophotometric readings over a 12-hour period. Among the formulations, the average particle size varied between 4.6 ± 0.1 µm and 6.3 ± 0.2 µm. The results revealed that all particles had spherical shape and non-aggregated microparticles were found on the formulation. It was also noticed that when double crosslinking was used in the production process, the encapsulation rate was higher when compared to the formulation without this approach. This result was also observed by the infrared and the XRD analyzes, both of which presented identity of specific functional groups of the drug in the formulations where CaCl2 was used. In addition, this approach allowed the mesalazine to be encapsulated at around 50%, a result not previously demonstrated by low molecular weight molecules using this technique. Another notable result was the retention of almost 40% of the drug content of the formulation, after 12 hours of dissolution testing. This was probably due to the high degree of crosslinking of the polymer. Therefore, the double crosslinking approach used to produce microparticles was effective to entrap mesalazine and can be used as a new alternative to encapsulate other molecules with similar physicochemical characteristics.