3D Printed Housing Devices for Segregated Compartmental Delivery of Oral Fixed-Dose Anti-Tubercular Drugs Adopting Print and Fill Strategy.

World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) disease. The absorption of RIF from an FDC incorporates INH, and it is significantly compromised due to its reaction with INH, resulting in a severe loss of RIF under gastric stomach pH condition. Such reduction in the dose of both drugs from FDC formulations has been alleged to be one of the chief obstacles in effective TB treatment. This emphasizes a need to develop suitable cutting-edge advanced bioengineered delivery devices that can attenuate this severe problem to mitigate this chief obstacle. Therefore, we designed, prototyped, and characterized bioengineered 3D printed housing devices in the form of printed tablets adopting print and fill strategy for segregated compartmental delivery of RIF into the intestine (to avoid stomach gastric pH induced chemical degradation as alone and FDC) and INH into the stomach (no degradation observed as alone and FDC in stomach gastric pH conditions) for the desired treatment outcome against TB. Prepared 3D printed housings showed almost zero friability, enough hardness along weight variations <±3.0%. Different thermal and morphological analyses confirmed the insignificant changes in the nature of the polymer as before and after printing. The in vitro release for INH from polyvinyl alcohol mediated 3D printed housings showed almost 100% release within 2.5 h in acidic medium, whereas poly-lactic acid (PLA) mediated 3D printed housings continued to release RIF above 70% in the presence of physiological enzymes in alkaline medium for 432 h. The in vivo bioavailability assessment correlated with in vitro dissolution behavior for INH and RIF, whereas RIF did not release from 3D printed PLA housings in vivo.

Extraction of small molecule from human plasma by prototyping 3D printed sorbent through extruded filament for LC-MS/MS analysis.

Analytical sample preparation techniques are regarded as crucial steps for analyzing compounds from different biological matrices. The development of new extraction techniques is a modern trend in the bioanalytical sciences. 3D printed techniques have emerged as a valuable technology for prototyping devices in customized shapes for a cost-effective way to advance analytical sample preparation techniques. The present study aims to fabricate customized filaments through the hot-melt extrusion (HME) technique followed by fused deposition modeling mediated 3D printing process for rapid prototyping of 3D printed sorbents to extract a sample from human plasma. Thus, we fabricated our own indigenous filament using poly (vinyl alcohol), Eudragit® RSPO, and tri-ethyl citrate through HME to prototype the fabricated filament into a 3D printed sorbent for the extraction of small molecules. The 3D sorbent was applied to extract hydrocortisone from human plasma and analyzed using a validated LC-MS/MS method. The extraction procedure was optimized, and the parameters influencing the sorbent extraction were systematically investigated. The extraction recovery of hydrocortisone was found to be >82% at low, medium, and high quality control samples, with a relative standard deviation of <2%. The intra-and inter-day precisions for hydrocortisone ranged from 1.0% to 12% and 2.0%-10.0%, respectively, whereas the intra-and inter-day accuracy for hydrocortisone ranged from 93.0% to 111.0% and 92.0% to 110.0%, respectively. The newly customizable size and shape of the 3D printed sorbent opens new possibilities for extracting small molecules from human plasma.

3D printing of immediate-release tablets containing olanzapine by filaments extrusion.

In this work, hot-melt extrusion (HME) is coupled with fused deposition modeling (FDM) mediated 3D printing to demonstrate additive manufacturing to fabricate immediate release (IR) prototypes of olanzapine with the aim of enhanced solubility using a fast disintegrating polymer (Kollicoat® IR). Drug-polymer solubility and interaction parameters were estimated by Hansen solubility parameters and Hildebrand-Scott equation. The obtained values signified drug-polymer miscibility. The detailed in vitro physicochemical evaluations of the developed filament through HME and its derived 3D printed tablet by FDM technique were assessed thoroughly by several analytical means such as light microscopy, DSC, XRD, FT-IR, SEM, etc. The average disintegration time of this developed 3D printed IR tablet was found to be 63.33 (±3.6) sec complying with the USP limit. Additionally, in vitro dissolution study data revealed almost close correlations and both showed 100% of drug release within 15 min, thus complying with the definition of IR tablet. Thus, this study demonstrates the feasibility of directly using olanzapine-Kollicoat® IR through the HME process without the addition of any plasticizers, organic solvents, etc. and coupling of HME with 3D printing technology allowing prototypes of IR tablet of olanzapine.

Extruded filaments derived 3D printed medicated skin patch to mitigate destructive pulmonary tuberculosis: design to delivery.

Background: Quercetin in combination with polyvinylpyrrolidone (PVP) was found to limit the spreading of necrosis to unaffected tissues in tuberculosis-infected mice. Therefore, we hypothesized that 3D printed medicated skin patch incorporated with a quercetin-PVP combination would provide an appropriate therapeutic drug concentration with desired sustained release profile.Research design and methods: We fabricated quercetin-PVP 40 extruded-filaments by hot-melt extrusion (HME) technique along with Eudragit® RSPO and tri-ethyl citrate and further printed it to make medicated skin patches using fused deposition modeling (FDM) based 3D Printing technology. Various characterizations were performed to optimize the 3D-printed patch formulation.Results: Patch formulation has been optimized for several characterization parameters and was further assessed using SEM, DSC, and XRD studies to confirm the conversion of crystalline quercetin into an amorphous form. Finally, the pharmacokinetic profile of an optimized patch was studied in rats showing prolonged Tmax, lowered Cmax, and reduced fluctuations in plasma concentrations till 18 days with single skin application of 3D-printed medicated patch.Conclusion: Overall data confirmed the feasibility of developing 3D printed medicated skin patches to provide plasma levels for continued 18 days in rats after a single application.