Formulating biopharmaceuticals using three-dimensional printing.

Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration (US FDA)-approved 3D printed tablet, there has been an increased interest in the application of this technology in drug delivery and biomedical applications. 3D printing brings us one step closer to personalized medicine, hence rendering the "one size fits all" concept in drug dosing obsolete. In this review article, we focus on the recent developments in the field of modified drug delivery systems in which various types of additive manufacturing technologies are applied.

Potential of Non-Contact Dynamic Response Measurements for Predicting Small Size or Hidden Damages in Highly Damped Structures.

Vibration-based structural health monitoring (SHM) is essential for evaluating structural integrity. Traditional methods using contact vibration sensors like accelerometers have limitations in accessibility, coverage, and impact on structural dynamics. Recent digital advancements offer new solutions through high-speed camera-based measurements. This study explores how camera settings (speed and resolution) influence the accuracy of dynamic response measurements for detecting small cracks in damped cantilever beams. Different beam thicknesses affect damping, altering dynamic response parameters such as frequency and amplitude, which are crucial for damage quantification. Experiments were conducted on 3D-printed Acrylonitrile Butadiene Styrene (ABS) cantilever beams with varying crack depth ratios from 0% to 60% of the beam thickness. The study utilised the Canny edge detection technique and Fast Fourier Transform to analyse vibration behaviour captured by cameras at different settings. The results show an optimal set of camera resolutions and frame rates for accurately capturing dynamic responses. Empirical models based on four image resolutions were validated against experimental data, achieving over 98% accuracy for predicting the natural frequency and around 90% for resonance amplitude. The optimal frame rate for measuring natural frequency and amplitude was found to be 2.4 times the beam's natural frequency. The findings provide a method for damage assessment by establishing a relationship between crack depth, beam thickness, and damping ratio.

Direct Granule Feeding of Thermal Droplet Deposition 3D Printing of Porous Pharmaceutical Solid Dosage Forms Free of Plasticisers.

PURPOSE: To develop a new direct granule fed 3D printing method for manufacturing pharmaceutical solid dosage forms with porous structures using a thermal droplet deposition technology. METHODS: Eudragit® E PO was used as the model polymer, which is well-known to be not FDM printable without additives. Wet granulation was used to produce drug loaded granules as the feedstock. The flow and feedability of the granules were evaluated. The physicochemical properties and in vitro drug release performance of the granules and the printed tablets were fully characterised. RESULTS: Using the method developed by this study, Eudragit E PO was printed with a model drug into tablets with infills ranging from 30-100%, without additives. The drug was confirmed to be molecularly dispersed in the printed tablets. The printing quality and performances of the porous tablets were confirmed to be highly compliant with the pharmacopeia requirement. The level of infill density of the porous tablets had a significant effect on their in vitro drug release performance. CONCLUSION: This is the first report of thermal droplet deposition printing via direct granule feeding. The results of this study demonstrated that this new printing method can be used as a potentially valuable alternative for decentralised pharmaceutical solid dosage form manufacturing.

A Low-Cost Multi-Sensor Data Acquisition System for Fault Detection in Fused Deposition Modelling.

Fused deposition modelling (FDM)-based 3D printing is a trending technology in the era of Industry 4.0 that manufactures products in layer-by-layer form. It shows remarkable benefits such as rapid prototyping, cost-effectiveness, flexibility, and a sustainable manufacturing approach. Along with such advantages, a few defects occur in FDM products during the printing stage. Diagnosing defects occurring during 3D printing is a challenging task. Proper data acquisition and monitoring systems need to be developed for effective fault diagnosis. In this paper, the authors proposed a low-cost multi-sensor data acquisition system (DAQ) for detecting various faults in 3D printed products. The data acquisition system was developed using an Arduino micro-controller that collects real-time multi-sensor signals using vibration, current, and sound sensors. The different types of fault conditions are referred to introduce various defects in 3D products to analyze the effect of the fault conditions on the captured sensor data. Time and frequency domain analyses were performed on captured data to create feature vectors by selecting the chi-square method, and the most significant features were selected to train the CNN model. The K-means cluster algorithm was used for data clustering purposes, and the bell curve or normal distribution curve was used to define individual sensor threshold values under normal conditions. The CNN model was used to classify the normal and fault condition data, which gave an accuracy of around 94%, by evaluating the model performance based on recall, precision, and F1 score.

Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion.

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10-30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion.

Geometric accuracy of an acrylonitrile butadiene styrene canine tibia model fabricated using fused deposition modelling and the effects of hydrogen peroxide gas plasma sterilisation.

BACKGROUND: Three-dimensional (3D) printing techniques have been used to produce anatomical models and surgical guiding instruments in orthopaedic surgery. The geometric accuracy of the 3D printed replica may affect surgical planning. This study assessed the geometric accuracy of an acrylonitrile butadiene styrene (ABS) canine tibia model printed using fused deposition modelling (FDM) and evaluated its morphological change after hydrogen peroxide (H2O2) gas plasma sterilisation. The tibias of six canine cadavers underwent computed tomography for 3D reconstruction. Tibia models were fabricated from ABS on a 3D printer through FDM. Reverse-engineering technology was used to compare morphological errors (root mean square; RMS) between the 3D-FDM models and virtual models segmented from original tibia images (3D-CT) and between the models sterilised with H2O2 gas plasma (3D-GAS) and 3D-FDM models on tibia surface and in cross-sections at: 5, 15, 25, 50, 75, 85, and 95% of the tibia length. RESULTS: The RMS mean ± standard deviation and average positive and negative deviation values for all specimens in EFDM-CT (3D-FDM vs. 3D-CT) were significantly higher than those in EGAS-FDM (3D-GAS vs. 3D-FDM; P < 0.0001). Mean RMS values for EFDM-CT at 5% bone length (proximal tibia) were significantly higher than those at the other six cross-sections (P < 0.0001). Mean RMS differences for EGAS-FDM at all seven cross-sections were nonsignificant. CONCLUSIONS: The tibia models fabricated on an FDM printer had high geometric accuracy with a low RMS value. The surface deviation in EFDM-CT indicated that larger errors occurred during manufacturing than during sterilisation. Therefore, the model may be used for surgical rehearsal and further clinically relevant applications in bone surgery.

3D Printing Technologies: Recent Development and Emerging Applications in Various Drug Delivery Systems.

The 3D printing is considered as an emerging digitized technology that could act as a key driving factor for the future advancement and precise manufacturing of personalized dosage forms, regenerative medicine, prosthesis and implantable medical devices. Tailoring the size, shape and drug release profile from various drug delivery systems can be beneficial for special populations such as paediatrics, pregnant women and geriatrics with unique or changing medical needs. This review summarizes various types of 3D printing technologies with advantages and limitations particularly in the area of pharmaceutical research. The applications of 3D printing in tablets, films, liquids, gastroretentive, colon, transdermal and intrauterine drug delivery systems as well as medical devices have been briefed. Due to the novelty and distinct features, 3D printing has the inherent capacity to solve many formulation and drug delivery challenges, which are frequently associated with poorly aqueous soluble drugs. Recent approval of Spritam® and publication of USFDA technical guidance on additive manufacturing related to medical devices has led to an extensive research in various field of drug delivery systems and bioengineering. The 3D printing technology could be successfully implemented from pre-clinical phase to first-in-human trials as well as on-site production of customized formulation at the point of care having excellent dose flexibility. Advent of innovative 3D printing machineries with built-in flexibility and quality with the introduction of new regulatory guidelines would rapidly integrate and revolutionize conventional pharmaceutical manufacturing sector.

High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling.

PURPOSE: This study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular dosage form design concepts. METHODS: FDM was used to generate ~0.5 mm thick discs of varying diameter (2-10 mm) from melt-extruded feedstocks based on 10% to 50% w/w felodipine in ethyl cellulose. Drug content was determined by UV spectroscopy and dispensing precision from printed disc mass. RESULTS: Mean felodipine content was within ±5% of target values for all print volumes and compositions including contents as high as ~50% w/w. However, poor dispensing precision was evident at all print volumes. CONCLUSIONS: In pursuit of dose flexibility, this successful demonstration of dose window extension using high content solid dispersions preserves FDM design flexibility by maintaining applicability to drugs of varying potencies. The achieved uniformity of content supports the application of varying content solid dispersions to modular dosage form concepts to enhance dose flexibility. However, poor dispensing precision impedes its utilisation until appropriate compatibility between FDM hardware and materials at varying drug contents can be attained.

3D Printed Sensors for Biomedical Applications: A Review.

This paper showcases a substantial review on some of the significant work done on 3D printing of sensors for biomedical applications. The importance of 3D printing techniques has bloomed in the sensing world due to their essential advantages of quick fabrication, easy accessibility, processing of varied materials and sustainability. Along with the introduction of the necessity and influence of 3D printing techniques for the fabrication of sensors for different healthcare applications, the paper explains the individual methodologies used to develop sensing prototypes. Six different 3D printing techniques have been explained in the manuscript, followed by drawing a comparison between them in terms of their advantages, disadvantages, materials being processed, resolution, repeatability, accuracy and applications. Finally, a conclusion of the paper is provided with some of the challenges of the current 3D printing techniques about the developed sensing prototypes, their corresponding remedial solutions and a market survey determining the expenditure on 3D printing for biomedical sensing prototypes.

Additive Manufacturing Technologies Used for Processing Polymers: Current Status and Potential Application in Prosthetic Dentistry.

There are 7 categories of additive manufacturing (AM) technologies, and a wide variety of materials can be used to build a CAD 3D object. The present article reviews the main AM processes for polymers for dental applications: stereolithography (SLA), digital light processing (DLP), material jetting (MJ), and material extrusion (ME). The manufacturing process, accuracy, and precision of these methods will be reviewed, as well as their prosthodontic applications.