Theophylline-Ethylcellulose Microparticles: Screening of the Process and Formulation Variables for Preparation of Sustained Release Particles

OBJECTIVE(S): The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of theophylline using ethylcellulose as the retardant material with high entrapment efficiency. MATERIALS AND METHODS: Microspheres were prepared by water-in-oil-in-oil (W/O(1)/O(2)) emulsion-solvent diffusion (ESD). A mixed solvent system consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were chosen as primary and secondary oil phases, respectively. In the current study formulations with different drug/polymer ratios were prepared and characterized by drug loading, loading efficiency, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). RESULTS: The best drug to polymer ratio was 0.5:1 (F(2) formulation). F(2) Formulation showed 29.53% of entrapment, loading efficiency of 88.59%, and mean particle size of 757.01 µm. SEM studies showed that the microspheres were spherical. FTIR, SEM, XRD and DSC showed that drug in the microspheres was stable and revealed crystallinity form. CONCLUSION: The results showed that, generally, an increase in the ratio of drug to polymer resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The release of theophylline was found to be diffusion controlled and was influenced by the drug to polymer ratio, loading efficiency, and particle size. The in vitro release profile could be modified by changing various processing and formulation parameters (as stirring rate, the volume of dispersing medium, and non-solvent concentration) to give a controlled release of drug from the microparticules.