3D-Printed Isoniazid Tablets for the Treatment and Prevention of Tuberculosis—Personalized Dosing and Drug Release

Abstract

The aim of the present work was to produce 3D-printed oral dosage forms with a sufficient drug dose displaying various release profiles. Hot-melt extrusion was utilized to produce drug-loaded feedstock material that was subsequently 3D-printed into 6, 8, and 10 × 2.5 mm tablets with 15% and 90% infill levels. The prepared formulations contained 30% (w/w) isoniazid in combination with one or multiple pharmaceutical polymers possessing suitable properties for oral drug delivery. Thirteen formulations were successfully hot-melt extruded of which eight had properties suitable for fused deposition modeling 3D printing. Formulations containing HPC were found to be superior regarding printability in this study. Filaments with a breaking distance below 1.5 mm were observed to be too brittle to be fed into the printer. In addition, filaments with high moisture uptake at high relative humidity generally failed to be printable. Different release profiles for the 3D-printed tablets were obtained as a result of using different polymers in the printed formulations. For 8 mm tablets printed with 90% infill, 80% isoniazid release was observed between 40 and 852 min. Drug release characteristics could further be altered by changing the infill or the size of the printed tablets allowing personalization of the tablets. This study presents novel formulations containing isoniazid for prevention of latent tuberculosis and investigates 3D printing technology for personalized production of oral solid dosage forms enabling adjustable dose and drug release properties.

Development of 3D Printed Tablets by Fused Deposition Modeling Using Polyvinyl Alcohol as Polymeric Matrix for Rapid Drug Release

“…Although higher drug loading in filaments could be obtained in these studies by melt extrusion, the drugs were, however, not molecularly dispersed in the PVA matrix and did not completely convert to amorphous form because the crushed filaments exhibited melting endotherms for drugs in differential scanning calorimetry (DSC) scans. 16,[36][37][38] It was mentioned in only one study 34 that the crystallinity of a model drug, calcein, either decreased or disappeared. In another study by Goyanes et al, 39 paracetamol appeared to be miscible with PVA at 4.3% and 8.2% concentrations, but not caffeine at either concentration; the authors attributed the difference to the ability of paracetamol to form hydrogen bonds with PVA.…”

Current formulation approaches in design and development of solid oral dosage forms through three-dimensional printing

“…Furthermore, the production of custom-made filaments introduces a more complex step to the relatively easy 3D printing process, requiring several optimisation studies to assess properties such as stiffness, toughness, melt viscosity and moisture uptake, usually altered by high drug loading [52,54]; filaments with unsuited mechanical properties can cause nozzle blockage and, therefore, printing failures [55].…”

“…3D printing can serve the purpose by manufacturing dosage forms with adjustable properties, e.g. bespoke drug dosages and/or release profiles [54,64]. Personalising medicinal products also encompasses features such as size, shape, texture, colour and flavour of oral dosage forms, all of which may influence patients' acceptability criteria [65][66][67].…”

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine

“…Many original 3D printing and biofabrication platforms ( Table 2) such as photolithography, inkjet printing, laser printing, robotic dispensing, and electrospinning are now available as standardized commercial systems [29,30] and have been reviewed extensively elsewhere. [5,19,31] These 3D printing platforms enable precision medicine through applications such as personalized implants, [3,[38][39][40] precision delivery of therapeutics [41][42][43][44][45][46][47][48][49][50] and precision in vitro screening models [51][52][53][54] (Figure 1D-F). Printed constructs may be utilized for these applications directly after fabrication, or may undergo postprocessing, including culture of constructs containing cellular components.…”