Design and optimization of pH-sensitive Eudragit nanoparticles for improved oral delivery of triclabendazole

Design of Experiments (DoE) techniques were used to identify and optimize the parameters involved in the formulation of triclabendazole pH-sensitive Eudragit (R) nanoparticles (NPs). Using a Placket Burmann design, Eudragit (R) E, Eudragit (R) RS, and two stabilizers (PVP and PVA) were evaluated for NPs formulation by nanoprecipitation. Based on the screening results, Eudragit E 100 (R) and PVP were selected as excipients, and their levels were studied and optimized using a central composite design, obtaining an optimum nanoparticulated system with a Size of 240 nm, a PDI of 0.420, and a ZP of 46.3 mV. Finally, a full characterization of the optimum system was carried out by XRD, DSC, equilibrium solubility, and dissolution rate in biorelevant mediums. As observed in XRD and DSC, the nanoencapsulation process produced a remarkable reduction in drug crystallinity that improved drug solubility and dissolution rate. Although more than 90% of TCBZ was dissolved in acidic mediums at 10 min, no increase in solubility or dissolution rate was observed in simulated saliva. Consequently, the development of pH-sensitive Eudragit (R) NPs would be a promising strategy in developing an immediate gastric release TCBZ formulation for oral delivery.

Automated summary

The Design of Experiments (DoE) techniques were used to optimize the formulation of triclabendazole nanoparticles, resulting in a pH-sensitive Eudragit (R) nanosystem with improved drug solubility and dissolution rate.