The commonly used methods for encapsulating hydrophilic molecules in nanoparticles (NPs) suffer from low encapsulation efficiency due to the drug rapidly being partitioned to the external aqueous phase. In the present study a new double emulsion solvent diffusion (DES-D) technique, resulted in particles with smaller size, lower size distribution and higher encapsulation efficiency. The utilization of partially water-miscible, class III organic solvent (ethyl acetate) enabled rapid diffusion

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... ugh the aqueous phase during evaporation, creating regions of local supersaturation near the interface. Smaller NPs were formed following phase transformations and polymer aggregation at these regions. Physicochemical characterization of the nanoparticles was performed by measuring particle size, zeta potential, drug entrapment efficiency, FTIR study and in vitro drug release. Batch G4 with encapsulation efficiency (EE) of 54 ± 3.6 % and Zeta potential of -28.0 mV was selected as an optimized batch. The stability of the optimized batch G4 indicated that formulation was stable at different storage conditions. FTIR studies indicated that there was no chemical interaction between drug and polymer.