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Design and optimization of pH-sensitive Eudragit nanoparticles for improved oral delivery of triclabendazole
Daniel Andrés Real1, Ailen Gagliano2, Nahuel Sonsini2
1Departamento de Química Farmacológica y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494 Santiago, Chile; Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile. Santos Dumont 964, Independencia, Santiago 8380494, Chile; Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
Abstract:
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 min, 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.
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