Micropartículas de acetato de celulose sintetizado a partir do Agave sisalana Perrine (Oriundo do semiárido brasileiro) para a obtenção de sistema de liberação controlada da sinvastatina

Abstract

Hypercholesterolemia represents one of the risk factors for the development and progression of atherosclerosis and consequently cardiovascular diseases, which are one of the main causes of morbidity and mortality in the world. Simvastatin, responsible for reducing the level of cholesterol in the blood, has low oral bioavailability (<5%), making it necessary to search for new controlled-release pharmaceutical preparations that can assist in the administration of this drug. Given this, one of the main focuses is on the production of polymeric systems, due to the characteristics that these forms guarantee to the drug when administered. Therefore, this work proposes to verify the feasibility of producing cellulose acetate matrix systems from cellulose extracted from Agave sisalana for controlled release of simvastatin. The microparticles were produced using the solvent emulsification-evaporation method, spray-dried using a polymer obtained from a natural product that was properly characterized by determining the degree of substitution (GS) of cellulose acetate chemically and by technique Nuclear Magnetic Resonance (NMR), in addition to determining its flow properties. The microparticles were characterized following the techniques of Optical Microscopy (OM), Scanning Electron Microscopy (SEM), Spectroscopy in the infrared region with Fourier transform (FT-IR), X-ray diffraction (XRD), Differential scanning calorimetry ( DSC), thermogravimetry (TGA) and determination of zeta potential and polydispersity index (PDI). Cellulose acetate showed good flow properties after the cellulose acetylation process, with GS chemically around 2.72 ± 0.27 and H-NMR of 3.49 confirming the formation of cellulose triacetate. The microparticles were spherical in shape with some deformities due to the drying process, with an average diameter between 1842 to 1857 nm, with a PDI of 0.278 and zeta potential around -4.45 mV. The thermal analyzes showed through the TGA a greater thermal stability for microparticles with the drug with a loss of mass of Δm = 37.15% between 205-327 ° C and for microparticles absent of the drug there was a loss of Δm = 56.00%. Through the DSC there was no phase transition of simvastatin, ensuring that it is in its amorphous state, homogeneously dispersed in the polymer matrix and compatible with the components of the formulation, as can be confirmed through XRD techniques that suggested changes in the crystalline network. of simvastatin to its amorphous state after its encapsulation observed in the reflections in the diffractograms. In the infrared spectrum, the absorption bands characteristic of the drug have shifted or been replaced by the polymer bands indicating trapping of simvastatin, with an encapsulation efficiency of 98% releasing in a controlled manner over a period of 72 hours, following the kinetic model of Higuchi. So until this stage, through obtaining all the results of the research, it can be concluded that the microparticles present great perspectives in the scope of new systems of release of simvastatin as a new proposal for the treatment of dyslipidemias.