Tuneable dissolution profile of tinidazole through thermoplastic polymer composites in low temperature 3D printing settings for pharmaceutical additive manufacturing applications.

Abstract

Thermoplastic polymeric materials are crucial for powder bed fusion (PBF) based three-dimensional (3D) printing in pharmaceuticals. However, due to limited availability and printability nature of the used feedstocks (either as powder bed materials or composites), underscoring a pressing demand for alternative solutions in pharmaceutical additive manufacturing applications. In this study, the first-time introduction of Kollidon® 25 (K25) thermoplastic polymer, which was not previously explored in PBF-based 3D printing technology, along with the simultaneous usage of Kollidon® SR (KSR) to form a thermoplastic polymer composite for the development of a tunable solid oral dosage form. In addition to this, a novel laser-absorbing dye, i.e. Pigment Green 7, was also introduced to facilitate the laser sintering process of the used thermoplastic polymer composites. Sintered tablets obtained from the used thermoplastic polymer bed composites were systematically characterized using various analytical tools andin vitroexaminations as well. The physicochemical characterization of all sintered tablet batches (B1-B7) was within the acceptable limit. Thermal and chemical analyses revealed no detrimental physical or chemical interactions between the components and sintered tablet batches after exposure to laser and temperature. Powder x-ray diffraction diffractograms suggested a change in the native state of tinidazole (TNZ, used as an active pharmaceutical ingredient) to amorphous due to the exposure to sintering parameters. Scanning electron microscopy micrographs of all batches showed intense fusion of the particles in the polymer composite. The sintered tablet batches B1 to B7 exhibited a drug content ranging from 90.36 ± 4.32% to 99.36 ± 1.24%. TNZ released in an acidic medium for up to 2.0 h from different sintered tablets were around 100% to 12% from B1 to B7 batches, respectively following alkaline medium for up to 12.0 h. TNZ release pattern was fine-tuned in accordance with the changes in the composition ratio of K25 and KSR polymers in order to get immediate release to sustained release. This prepared unique thermoplastic pharmaceutical grade polymer composite might broaden the range of materials accessible for PBF-mediated 3D printing in pharmaceutical industrial applications in near future.