Development of multiple structured extended release tablets via hot melt extrusion and dual-nozzle fused deposition modeling 3D printing.

The study aims to fabricate extended release (ER) tablets using a dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing technology based on hot melt extrusion (HME), using caffeine as the model compound. Three different ER tablets were developed, which obtained "delayed-release", "rapid-sustained release", and "release-lag-release" properties. Each type of tablet was printed with two different formulations. A novel printing method was employed in this study, which is to push the HME filament from behind with polylactic acid (PLA) to prevent sample damage by gears during the printing process. Powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) results showed that caffeine was predominately amorphous in the final tablets. The dissolution of 3D printed tablets was assessed using a USP-II dissolution apparatus. ER tablets containing PVA dissolved faster than those developed with Kollicoat IR. Overall, this study revealed that ER tablets were successfully manufactured through HME paired with dual-nozzle FDM 3D printing and demonstrated the power of 3D printing in developing multi-layer tablets with complex structures.

Fabrication of timed-release indomethacin core-shell tablets for chronotherapeutic drug delivery using dual nozzle fused deposition modeling (FDM) 3D printing.

In the present study, timed-release indomethacin tablets, releasing drug after predetermined lag times, were developed for the effective treatment of early morning stiffness in rheumatoid arthritis using two-nozzle fused deposition modeling (FDM) 3D printing with a Bowden extruder. The developed core-shell tablets consisted of a drug-containing core and release-regulating shell with different designed thicknesses (i.e., 0.4 mm, 0.6 mm, 0.8 mm). The filaments to fabricate cores and shells were prepared using hot-melt extrusion (HME), and different filament compositions were formulated for core tablets and screened for rapid release and printability. Eventually, the HPMCAS-based formulation comprised a core tablet enclosed by a shell of Affinisol™ 15LV, a swellable polymer. During 3D printing, one nozzle was dedicated to printing core tablets loaded with indomethacin, and the other nozzle was dedicated to printing shells, making a whole structure produced at once without inconvenient filament change and nozzle cleanout. The mechanical properties of filaments were compared using a texture analyzer. The core-shell tablets were characterized for dissolution profiles and physical attributes (e.g., dimension, friability, hardness). SEM image indicated a smooth and complete surface of the core-shell tablets. The tablets showed 4-8 h of lag depending on the shell thicknesses and released most of the drugs in 3 h, regardless of the shell thicknesses. The core-shell tablets showed high reproducibility but exhibited low dimensional accuracy in the shell thickness. This study explored the suitability of using two-nozzle FDM 3D printing with Bowden extrusion for producing personalized chronotherapeutic core-shell tablets and discussed possible challenges that needed to be considered for a successful printing process using this technology.

Fabrication of bilayer tablets using hot melt extrusion-based dual-nozzle fused deposition modeling 3D printing.

The objective of this study was to fabricate bilayer tablets using hot-melt extrusion (HME)-based dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing techniques. Acetaminophen (APAP) and caffeine citrate (CC) were used as the model drugs. Five bilayer tablets with different formulations were developed and two different structures were printed for each formulation. Three-point bending, Hooke's law, and resistance and stiffness tests were conducted to determine the mechanical properties of the filaments. A novel method, 3D printed tablet retention rate, was developed and used for the first time to compare the printing quality of different filaments. The 3D printed tablets were evaluated to derive the drug release rates using a USP-II dissolution apparatus. HPMC HME 15LV and HPMCAS-LG were identified as good printing materials; however, HPMC HME 100LV was not suitable for printing under frequent nozzle switching conditions. Although mechanical characterization tests can be used to determine whether filaments can be printed, they cannot specifically distinguish the quality of printing between the filaments. Overall, this study revealed the successful fabrication of bilayer tablets via HME paired with dual-nozzle FDM 3D printing.

Maternal Nicotine Exposure During Late Gestation and Lactation Increases Anxiety-Like and Impulsive Decision-Making Behavior in Adolescent Offspring of Rat.

Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.