Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method

Abstract

The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres were prepared by using water-in-oil-in-oil (W/O 1 /O 2 ) double-emulsion solvent diffusion method, using different ratios of ethylcellulose to tolmetin sodium. Span 80 was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties, drug content, loading efficiency, production yield, and particle size. Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to characterize microparticles. The in vitro release studies were performed in pH 1.2 and 7.4. The prepared microspheres were spherical in shape. The drug-loaded microspheres showed near to the theoretical of entrapment and release was extended up to 24. The X-ray diffractogram and differential scanning thermographs showed amorphous state of the drug in the microspheres. It was shown that the drug: polymer ratio, stirring rate, volume of dispersing medium and surfactant influenced the drug loading, particle size and drug release behavior of the formed microparticles. The results showed that, generally, an increase in the ratio of drug: polymer (0.5:1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The in vitro release profile could be modified by changing various processing and formulation parameters to give a controlled release of drug from the microparticules. The release of tolmetin was influenced by the drug to polymer ratio and particle size and was found to be diffusion and erosion controlled. The best-fit release kinetic was achieved with Peppas model.