AN INNOVATIVE AND SCALABLE METHOD OF GELATION IONOTROPIC TO PRODUCE CHITOSAN NANOPARTICLES BY MEMBRANE PROCESS

Ionotropic gelation (IG) is based on the capability of polyelectrolytes to crosslink in the presence of counter ions forming polymeric nanoparticles. The method is most frequently used for the preparation of chitosan nanoparticles (CS) and it has several advantages such as the use of aqueous solutions, the preparation of particles in the nanometric range of size, the control of particle size by the variation of parameters such as chitosan and TPP concentrations and the possibility to encapsulate a large variety of molecules. Although IG is well studied at laboratory scale its application at large scale is still under investigation. In the present work, for the first time, a new scalable IG process by membrane technology was developed to produce chitosan nanoparticles using tripolyphosphate (TPP) as a cross-linking agent. For the purpose, the two phases, one containing chitosan and the other containing TPP were put in contact by using a tubular SPG hydrophobic membrane with a pore diameter of 1 µm. TPP permeated through the membrane pores into the lumen side along which the chitosan solution flowed in continuous single-pass or recirculated operation mode. The influence of formulation factors (concentration of chitosan and TPP solutions, pH of the chitosan solution, volume ratio) and process parameters (axial velocity, dispersed and continuous phase flow rate) on zeta potential, mean particle size and polydispersity index of chitosan nanoparticles was studied. The membrane process allowed us to produce chitosan nanoparticles in the range of size between 170 and 300 nm and with a polydispersity index close to 0.2.