Digital Light Processing (DLP) 3D Printing of Atomoxetine Hydrochloride Tablets Using Photoreactive Suspensions

Abstract

Three-dimensional (3D) printing technologies are based on successive material printing layer-by-layer and are considered suitable for the production of dosage forms customized for a patient’s needs. In this study, tablets of atomoxetine hydrochloride (ATH) have been successfully fabricated by a digital light processing (DLP) 3D printing technology. Initial materials were photoreactive suspensions, composed of poly(ethylene glycol) diacrylate 700 (PEGDA 700), poly(ethylene glycol) 400 (PEG 400), photoinitiator and suspended ATH. The amount of ATH was varied from 10.00 to 25.00% (w/w), and a range of doses from 12.21 to 40.07 mg has been achieved, indicating the possibility of personalized therapy. The rheological characteristics of all photoreactive suspensions were appropriate for the printing process, while the amount of the suspended particles in the photoreactive suspensions had an impact on the 3D printing process, as well as on mechanical and biopharmaceutical characteristics of tablets. Only the formulation with the highest content of ATH had significantly different tensile strength compared to other formulations. All tablets showed sustained drug release during at least the 8h. ATH crystals were observed with polarized light microscopy of photoreactive suspensions and the cross-sections of the tablets, while no interactions between ATH and polymers were detected by FT-IR spectroscopy.

Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

“…To date, DLP printers have been exploited to produce tablets and hydrogels containing different drugs, e.g., ATH [ 30 ], theophylline [ 27 ], ibuprofen [ 28 ], paracetamol [ 29 ] and sulforhodamine B [ 31 ], polymers/mixtures of polymers, including PEGDA, PEG 300 and PEG 400, and photoinitiators (PI) such as Irgacure 2959, riboflavin and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (DPPO). Unlike commercially available resins, when it comes to the printing of the dosage forms, it is necessary to establish optimal printing parameters for each formulation separately, in order to ensure good adhesion of the tablets to the building platform and to avoid significant variations in tablet dimensions and consequently drug loading [ 14 , 28 ].…”

“…The working wavelength of the Wanhao Duplicator 8 3D printer used in this study is 405 nm. The same working wavelength was used in our previous studies, where the model drugs were ibuprofen [ 28 ] and ATH [ 30 ]. Both of the studies demonstrated that no drug degradation occurred during the 3D-printing process.…”

“…The diameter of the fabricated tablets varied to a greater extent with respect to their thickness, especially with the increase of the amount of ATH in the formulations. This can be explained by the larger amount of suspended particles and their scattering phenomena onto the light beam [ 30 ]. Additionally, greater variation in diameter in comparison to the designed 3D model was observed for 2-mm- and 3-mm-thick tablets, which can be attributed to the longer exposure time needed for their successful printing.…”

“…Content of ATH varied from 5.00% to 20.00% ( w / w ), while a 3:1 ratio of PEGDA/PEG 400 was the same in all formulations in order to obtain tablets with appropriate mechanical and release properties, based on a previously published study [ 30 ]. All formulations contained 10% water and 0.10% DPPO.…”

“…The study demonstrated that the addition of mannitol, sodium chloride and poly(ethylene glycol) 400 (PEG 400) increased paracetamol release from printed tablets, with a different effect on mechanical characteristics of tablets [ 29 ]. In another study, Krkobabic et al demonstrated successful DLP printing with an active substance suspended in photopolymer mixture [ 30 ]. In a study by Larush et al, pH-responsive hydrogels loaded with sulforhodamine B were produced using DLP 3D printing [ 31 ].…”