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

Document Type : Original Article


1 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

3 Biotechnology Center, Tabriz University of Medical Sciences, Tabriz, Iran


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/O1/O2) 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).
The best drug to polymer ratio was 0.5:1 (F2 formulation). F2 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.
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.


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