3D printed benznidazole tablets based on an interpolyelectrolyte complex by melting solidification printing process (MESO-PP): An innovative strategy for personalized treatment of Chagas disease

Abstract

3D printing technology is revolutionizing pharmaceuticals, offering tailored solutions for solid dosage forms. This innovation is particularly significant for conditions like Chagas disease, which require weight-dependent treatments. In this work, a formulation of benznidazole (BNZ), the primary treatment for this infection, was developed to be utilized with the Melting Solidification Printing Process (MESO-PP) 3D printing technique. Considering the limited aqueous solubility of BNZ, an interpolyelectrolyte complex (IPEC), composed of chitosan and pectin, was integrated to improve its dissolution profile. The formulations, also called inks in this context, with and without IPEC were integrally characterized and compared. The printing process was studied, the releaseof BNZ from 3D-prints (3DP) was exhaustively analyzed and a physiologically based pharmacokinetic model (PKPB) was developed to forecast their pharmacokinetic performance. 3DP were successfully achieved loading 25, 50 and 100 mg of BNZ. The presence of the IPEC in the ink caused a decrease in the crystalline domain of BNZ and facilitated the printing process, reaching a print success rate of 83.3 %. Interestingly, 3DP-IPEC showed accelerated release dissolution profiles, releasing over 85 % of BNZ in 90 min, while 3DP took up to 48 h fordoses above 25 mg. The PBPK model demonstrated that 3DP-IPEC tablets would present high bioavailability (0.92), higher than 3DP (0.36) and similar to the commercial product. This breakthrough holds immense potential for improving treatment outcomes for neglected diseases.