3D printing as a solution for tablet splitting challenges dedicated to the Chagas disease treatment

Abstract

Chagas disease is a potentially fatal neglected infection affecting both infants and adults. Currently, only benznidazole (BNZ) and nifurtimox (NFX) are approved for the treatment, and there is a considerable need for dosage adjustments to meet individual patient conditions. However, as the commercial options are limited, splitting commercial tablets of BNZ and NFX is common practice. Thus, this study aimed to evaluate, for the first time, the splitting behavior of such commercial tablets. Average mass, drug content, friability, and hardness were evaluated using two subdivision methods. Additionally, an in-use stability of split tablets was performed. Lastly, BNZ and NFX tablets produced by 3D printing with different dosages were proposed as an alternative method of personalizing treatment. The findings of this work indicated that the subdivision method was not a relevant variable in obtaining halves, although the splitting device was shown to deliver better results in obtaining quarters. In-use stability demonstrated that the split tablets were chemically preserved under forced storage conditions for at least 15 days. Even though moisture adsorption occurred, no changes in drug characteristic signals in the infrared spectra were observed. The physical and mechanical properties were compromised after splitting, leading to multiple fragmentation. In addition, the high variation in mass and mass loss led to high dosage variations and, consequently, may increase the treatment risk. Therefore, splitting these tablets into quarters should be discouraged. Thus, BNZ and NFX 3D printing tablets were prepared to avoid the splitting issues of the marketed tablets. This approach proves to be a promising option to minimize the risks associated with tablet splitting while providing a more reliable and flexible method for dose adjustment.