Preparo, caracterização e perfil de liberação in vitro de microesferas de sílica processadas por spray drying

Abstract

In this study, the release rate of cyanocobalamin from different sol-gel spray-dried silica microspheres formulations was investigated. The drug was incorporated into a sol phase of a silica precursor, tetraethyl orthosilicate (TEOS), before spray drying with a Büchi laboratory scale equipment. The effects of the sol phase pH, the drug loading, thewater/alkoxide ratio of sol as well as polyethylene glycol (Mw 6000) influence (hybrid microspheres) on the release behavior of drug and characteristics of microspheres were investigated. The microspheres were carefully characterized with Fourier transform infrared spectroscopy (FTIR), thermal analyze (TGA, DSC), helium picnometry, laser diffractometry, microanalyses (EDS) and scanning electron microscopy (SEM), X-ray diffraction (XRD), high performance liquid chromatography (HPLC), nitrogen sorption measurements (BET) and in vitro release. Spray drying showed that it is a promising way to produce spherical silica gel particles with a narrow particle size range for controlled delivery of cyanocobalamin. Silica gel microspheres had a smooth surface. Microparticles prepared from diluted sol (Rw=42) showed some structures aggregated, clustered and empty. The release from samples into dialyzes sacs showed a burst effect in the sixth day and, after that, a slow release period. Although, when the assay was performed withoutdialyze bag the most important release of drug occurred in 24h. It showed that dialyze sac had its own influence on the release rate of the system. The water/alkoxide ratios used under experimental conditions did not influence the cyanocobalamin release rate from the spray-dried silica microspheres. The slow release was associated with a very small BETsurface area and the data obtained here also suggested that the possible rate-limiting step of release was the saturation of bulk solution with silica resulting in the inhibition of both erosion of matrix and diffusion of drug.