Preparation and Evaluation of Poly (s-caprolactone) Nanoparticles-in- Microparticles by W/O/W Emulsion Method

Objective(s) Theophylline, a xanthenes derivative, is still widely used as an effective bronchodilator in the management of asthmatic patients. It is used both as a prophylactic drug and to prevent acute exacerbations of asthma. The aim of study was to formulate and evaluate effect of the microencapsulation of theophylline loaded nanoparticles on the reduction of burst release. Materials and Methods Microparticles (simple and composite) and nanoparticles were prepared by using water-in-oil-in-water (W۱/O/W۲ double-emulsion solvent diffusion/evaporation method), taking different ratios of drug/polymer. Solvent systems consist of ethyl acetate and dichloromethane for microspheres and nanospheres, respectively. In the current study formulations were characterized by loading efficiency, yield, particle size, zeta potential, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Results In microparticles, the best drug to polymer ratio was ۰.۸:۱ (F۳). F۳ formulation had minimum burst effect (۳۷.۸۱%), high loading efficiency (۹۵.۸۸%). In nanoparticles, F۴ formulation (۰.۴:۱ drug/polymer ratio) showed high production yield (۴۰.۸%), loading efficiency (۹۹.۰۵%), low particle size (۷۵۶ nm) and minimum burst effect compared with other nanoparticle formulations. The drug loaded composite microspheres (F۹) showed minimum burst effect, acceptable release and mean particle size ۱۷.۶۹۶ pm. The XRD and DSC showed stable character of theophylline in the drug loaded microspheres. The drug release was found to be diffusion and erosion controlled. Conclusion The burst was significantly lower with composite microparticles and may be explained by lower diffusion of the drug from double polymeric wall formed by the nanoparticles matrix followed by another diffusion step through the microparticle polymeric wall.

Keywords:

Burst Effect , Composite Microparticle , Double-Emulsion , Ethylcellulose , Nanoparticle , Poly (s-caprolactone)