3D-printed Gabapentin-loaded Implants for Sustained Release: Leveraging 3D Printing and Hot Melt Extrusion (HME) for Customizable Drug Delivery.

3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release

Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process.

Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500N) and very large particle size (> 1mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5min (% Sext) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30min and % Sext < 15 was achieved with egglets of 6mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation.

Hot melt extrusion (HME) helps to improve the solubility of BCS class II and IV molecules. The downstream processing of the resulting filaments was crucial in developing the final dosage form. The present work investigates advantages of combining HME with fused deposition modelling (FDM) 3-Dimensional (3D) printing in delivering the naringenin to the colon to treat inflammatory bowel disease. HME filaments were made using a pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate for the localized delivery of naringenin at the colonic pH. Polyethylene glycol (PEG - 4000) and Aerosil 200 were incorporated as plasticizer and flow modulator respectively, to facilitate the extrusion process. Naringenin was converted to amorphous form as confirmed by differential scanning calorimetry and powder x-ray diffraction. The optimized filament showed 0.03, 11.52 and 77.80% drug release at pH 1.2, 6.8 and 7.4 respectively. The tablets produced with the optimized filament by compression and 3D printing also confirmed the presence of naringenin in amorphous form and demonstrated pH-dependent release followed by zero-order release independent of the concentration. The dissolution profiles of FDM 3D printed (3DP) tablets with varying dimensions and infill densities suggested that both significantly influenced drug release from the tablets without altering the composition of tablets, indicating the potential application of 3D printing technology in developing personalized medicine according to patient requirements. These promising results may be valuable in evaluating the potential of naringenin in animal models, which may further facilitate clinical applications.

This study aimed to develop an amorphous solid dispersion (ASD) of fenofibrate using Hot Melt Extrusion (HME) and 3D printing to evaluate the impact of preparation methods on ASD properties. Fenofibrate (10% w/w) was processed with Soluplus® and Polyethylene oxide-N80 to produce HME filaments. These filaments were either used as feedstock for Fused Deposition Modeling (FDM) 3D printing to fabricate tablets with 90%, 70%, and 50% infill densities or milled and filled into gelatin capsules. Printability was assessed via a three-point bend test. The fenofibrate formulations were evaluated for drug content, physical state, surface morphology, and release profile. The SEM images of pure fenofibrate showed large cylindrical crystals while the 3D-printed tablets showed a smooth surface with no record of any crystals. This observation is in line with the DSC results and confirms the conversion of fenofibrate from crystalline to an amorphous state. The in- vitro drug release for the 3D printed tablets and capsules was increased 2-fold as compared to pure fenofibrate. Statistical comparisons further supported these findings, highlighting infill density as a tunable parameter for modulating release kinetics.

Preparation and characterization of hot-melt extruded polycaprolactone-based filaments intended for 3D-printing of tablets

A comprehensive overview of extended release oral dosage forms manufactured through hot melt extrusion and its combination with 3D printing

Fused deposition modeling 3D printing of solid oral dosage forms containing amorphous solid dispersions: How to elucidate drug dissolution mechanisms through surface spectral analysis techniques?

Hot Melt Extrusion (HME) is a continuous pharmaceutical manufacturing process that has been extensively investigated for solubility improvement and taste masking of active pharmaceutical ingredients. Recently, it is being explored for its application in 3D printing. 3D printing of pharmaceuticals allows flexibility of dosage form design, customization of dosage form for personalized therapy and the possibility of complex designs with the inclusion of multiple actives in a single unit dosage form. Fused Deposition Modeling (FDM) is a 3D printing technique with a variety of applications in pharmaceutical dosage form development. FDM process requires a polymer filament as the starting material that can be obtained by hot melt extrusion. Recent reports suggest enormous applications of a combination of hot melt extrusion and FDM technology in 3D printing of pharmaceuticals and need to be investigated further. This review in detail describes the HME process, along with its application in 3D printing. The review also summarizes the published reports on the application of HME coupled with 3D printing technology in drug delivery.

3D printing technology is gaining attention as a next-generation approach to drug formulation. Among 3D printing techniques, fused deposition modeling is cost-effective but depends heavily on suitable filaments. Hot melt extrusion enables filament production by incorporating poorly water-soluble drugs like cyclosporine A into polymers to form solid dispersions. However, achieving immediate release formulations with 3D printing remains challenging due to issues such as inadequate tablet disintegration or drug entrapment within the polymer matrix. This study aimed to develop and evaluate immediate release 3D-printed cyclosporine A tablets using HME filaments. Three parameters were modified in the 3D printing process: varying fill speeds, infill densities, and channel lengths. Filaments composed of Kollidon® VA 64 and HPC–SSL (1:1) were used to print tablets. Solid-state analysis confirmed cyclosporine A ‘s amorphous state and partial crystallinity in Xylisorb® 300. Dissolution studies revealed that lower infill densities (30%) and fewer walls enhanced drug release by increasing internal void space and reducing hardness. Conversely, greater tablet height (channel length) delayed dissolution. These findings emphasize the critical role of geometric design in drug release, showcasing the potential of 3D printing to create personalized dosage forms tailored to patient needs by optimizing structural parameters.

This research paper provides an in-depth examination of the mechanical characteristics of 3D-printed specimens made from acrylonitrile butadiene styrene (ABS) and resins akin to ABS, with a focus on two widely used 3D printing methodologies: fused deposition modeling (FDM) and stereolithography (SLA). The study investigates how variations in 3D printing technology and infill density impact mechanical parameters such as Young’s modulus, tensile strength, strain, nominal strain at break, maximum displacement, and maximum force at break. Tensile testing was conducted to assess these critical parameters. The results indicate distinct differences in mechanical performance between FDM- and SLA-printed specimens, with SLA consistently showing superior mechanical parameters, especially in terms of tensile strength, displacement, and Young’s modulus. SLA-printed specimens at 30% infill density exhibited a 38.11% increase in average tensile strength compared to FDM counterparts and at 100% infill density, a 39.57% increase was observed. The average maximum displacement for SLA specimens at 30% infill density showed a 14.96% increase and at 100% infill density, a 30.32% increase was observed compared to FDM specimens. Additionally, the average Young’s modulus for SLA specimens at 30% infill density increased by 17.89% and at 100% infill density, a 13.48% increase was observed, highlighting the superior mechanical properties of SLA-printed ABS-like resin materials. In tensile testing, FDM-printed specimens with 30% infill density showed an average strain of 2.16% and at 100% infill density, a slightly higher deformation of 3.1% was recorded. Conversely, SLA-printed specimens at 30% infill density exhibited a strain of 2.24% and at 100% infill density, a higher strain value of 4.15% was observed. The comparison suggests that increasing the infill density in FDM does not significantly improve deformation resistance, while in SLA, it leads to a substantial increase in deformation, raising questions about the practicality of higher infill densities. The testing data underscore the impact of infill density on the average nominal strain at break, revealing improved performance in FDM and significant strain endurance in SLA. The study concludes that SLA technology offers clear advantages, making it a promising option for producing ABS and ABS-like resin materials with enhanced mechanical properties.

Introduction This study aims to develop immediate release tablet formulations of lornoxicam (LRX) using hot melt extrusion (HME)-based fused deposition modeling (FDM) focusing on the adjustment of drug release by arranging infill densities and evaluating microcrystalline cellulose II (MCC II) as a disintegrating agent for HME-FDM purposes. LRX is a poorly soluble drug that exhibits pH-dependent solubility with a high thermal degradation temperature. These characteristics make it an ideal model drug for the HME-based FDM technique. Methods Various filament formulations were extruded using an extruder, and suitable filaments were used to produce 3D-printed tablets. Filaments and tablets were characterized. Dissolution studies were performed on tablets with different infill densities. DSC, FTIR, XRD, and SEM analyses were conducted. Results Although the solubility of LRX increases with pH, disintegrating agents such as MCC II had a more significant effect on the dissolution of LRX than sodium bicarbonate, which was used as the alkalinizing pore-forming agent. Dissolution studies revealed that the dissolution of LRX was enhanced by tablet erosion. Tablet erosion increased as the infill density decreased, and an immediate release profile was reached with tablets having 25% infill density. Despite the availability of conventional immediate release LRX tablets, this newly developed formulation offers the potential to be modulated for personalized therapy via the 3D printing technique. Conclusion This study demonstrates the feasibility of HME-based FDM printing technology for producing immediate-release LRX tablets with consistent quality, highlighting the utilization of MCC II as a disintegrating agent that enhances LRX dissolution in this process.

3D printed bilayer tablet with dual controlled drug release for tuberculosis treatment.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability

Three-dimensional (3D) printing of pharmaceuticals has been centered around the idea of personalized patient-based ‘on-demand’ medication. Fused deposition modeling (FDM)-based 3D printing processes provide the capability to create complex geometrical dosage forms. However, the current FDM-based processes are associated with printing lag time and manual interventions. The current study tried to resolve this issue by utilizing the dynamic z-axis to continuously print drug-loaded printlets. Fenofibrate (FNB) was formulated with hydroxypropyl methylcellulose (HPMC AS LG) into an amorphous solid dispersion using the hot-melt extrusion (HME) process. Thermal and solid-state analyses were used to confirm the amorphous state of the drug in both polymeric filaments and printlets. Printlets with a 25, 50, and 75% infill density were printed using the two printing systems, i.e., continuous, and conventional batch FDM printing methods. Differences between the two methods were observed in the breaking force required to break the printlets, and these differences reduced as the infill density went up. The effect on in vitro release was significant at lower infill densities but reduced at higher infill densities. The results obtained from this study can be used to understand the formulation and process control strategies when switching from conventional FDM to the continuous printing of 3D-printed dosage forms.