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® nanoparticles (NPs). Using a Placket Burmann design, Eudragit® E, Eudragit® RS, and two stabilizers (PVP and PVA) were evaluated for NPs formulation by nanoprecipitation.
Based on the screening results, Eudragit E 100® 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 minutes, no increase in solubility or dissolution rate was observed in simulated saliva. Consequently, the development of pH-sensitive Eudragit® NPs would be a promising strategy in developing an immediate gastric release TCBZ formulation for oral delivery.
Article information: Daniel Andrés Real, Ailen Gagliano, Nahuel Sonsini, Gaspar Wicky, Lucas Orzan, Darío Leonardi, Claudio Salomon, Design and optimization of pH-sensitive Eudragit nanoparticles for improved oral delivery of triclabendazole, International Journal of Pharmaceutics, 2022. https://doi.org/10.1016/j.ijpharm.2022.121594.