Electromagnetic drop-on-demand (DoD) technology as an innovative platform for amorphous solid dispersion production.

Production of amorphous solid dispersions (ASDs) is an effective strategy to promote the solubility and bioavailability of poorly water soluble medicinal substances. In general, ASD is manufactured using a variety of classic and modern techniques, most of which rely on either melting or solvent evaporation. This proof-of-concept study is the first ever to introduce electromagnetic drop-on-demand (DoD) technique as an alternative solvent evaporation-based method for producing ASDs. Herein 3D printing of ASDs for three drug-polymer combinations (efavirenz-Eudragit L100-55, lumefantrine-hydroxypropyl methylcellulose acetate succinate, and favipiravir-polyacrylic acid) was investigated to ascertain the reliability of this technique. Polarized light microscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Fourier Transform  Infrared (FTIR) spectroscopy results supported the formation of ASDs for the three drugs by means of DoD 3D printing, which significantly increases the equilibrium solubility of efavirenz from 0.03 ± 0.04 µg/ml to 21.18 ± 4.20 µg/ml, and the equilibrium solubility of lumefantrine from 1.26 ± 1.60 µg/ml to 20.21 ± 6.91 µg/ml. Overall, the reported findings show how this new electromagnetic DoD technology can have a potential to become a cutting-edge 3D printing solvent-evaporation technique for on-demand and continuous manufacturing of ASDs for a variety of drugs.

Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

3D printing of biologics-what has been accomplished to date?

Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.

Unraveling the influence of solvent composition on Drop-on-Demand binder jet 3D printed tablets containing calcium sulfate hemihydrate.

Recently, binder jet printed modular tablets were loaded with three anti-viral drugs via Drop on Demand (DoD) technology where drug solutions prepared in ethanol showed faster release than those prepared in water. During printing, water is used as a binding agent, whereas ethanol is added to maintain the porous structure of the tablets. Thus, the hypothesis is that the porosity would be controlled by manipulating the percentage of water and ethanol. In this study, Rhodamine 6G (R6G) was selected as a model drug due to its high solubility in water and ethanol, visualization function as a fluorescent dye, and potential therapeutic effects for cancer treatment. Approximately, 10 mg/ml R6G solutions were prepared with five different water-ethanol ratios (0-100, 75-25, 50-50, 75-25, 100-0). The ink solutions were printed onto blank binder jet 3D-printed tablets containing calcium sulphate hemihydrate using DoD technology. The tablets were dried at room temperature and then characterized using SEM-EDX, fluorescent microscope, TGA, XRD, FTIR, and DSC as well as in vitro release studies to investigate the impact of water-ethanol ratio on the release profile of R6G. Results indicated that the solution with higher ethanol ratio penetrated the tablets faster than the lower ethanol ratio, while the solution prepared with pure water was first accumulated onto the tablets' surface and then absorbed by the tablets. Moreover, tablets with more water content gained more weight and thickness. The EDX analysis and fluorescent microscope showed the uniform surface distribution of the drug. The SEM images revealed the difference in the tablet surface among the five formulations. Furthermore, the TGA data presents a notable increase in water loss, with XRD analysis suggesting the formation of gypsum in tablets containing elevated water content. The release study exhibited that the fastest release was from WE0-100, whereas the release rate decreases as the content of water increases. The WE0-100 releases more than 40 % drug within the first hour which is almost twice as high of the WE100-0 formulation. This DoD technology could distribute drugs onto the tablet's surface uniformly. The calcium sulfate would transform from hemihydrate to dihydrate form in the presence of water and therefore, those tablets treated with higher water content led to slower release. In conclusion, this study underscores the substantial impact of the water-ethanol ratio on drug release from binder jet printed tablets and highlights the potential of DoD technology for uniform drug distribution and controlled release.

Twin-screw extrusion of vitamin D3/iron-blend granules in corn and lentil composite flours: Stability, microstructure, and interaction of vitamin D3 with human osteoblast cells.

Vitamin D3 (VD3) and iron-blend granules were blended with corn and lentil composite flour (75/25, w/w) and fed into a pilot-scale twin-screw extruder to produce ready-to-eat snacks. The morphology and microstructure of extruded snacks were examined using scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), X-ray powder diffraction, and FT-IR. Differential scanning calorimetry and thermogravimetric analysis measured the melting temperature and thermal stability of the extrudates. SEM and FT-IR analysis demonstrate that micronutrients are mixed well in formulations used in extrudates at high shear and high temperatures. The SEM-EDX exhibited the presence of iron, whereas high performance liquid chromatography measurements confirmed the significant retention of VD3 in the extruded snacks. The interaction between VD3 and human osteoblast cells was studied using live imaging and the MMT assay. Overall, for the first time, VD3 and Fe2+ blend granules have been used in an extrusion platform, which has significant potential for the intervention of VD3 and iron deficiencies. PRACTICAL APPLICATION: For the first time, we reported the use of VD3/iron-blend granules in extruded products. The findings of this work demonstrated the thermal stability and capability of providing adequate quantities of VD3 and iron in corn flour/lentil flour/VD3-iron blend extruded snacks. Furthermore, the interaction of VD3 with osteoblast cells highlights the potential health benefits of the extrudates.

A Proof-of-Concept Preparation of Lipid-Plasmid DNA Particles Using Novel Extrusion-Based 3D-Printing Technology, SMART.

Gene therapy is a promising approach with delivery of mRNA, small interference RNA, and plasmid DNA to elicit a therapeutic action in vitro using cationic or ionizable lipid nanoparticles. In the present study, a novel extrusion-based Sprayed Multi Adsorbed-droplet Reposing Technology (SMART) developed in-house was employed for the preparation, characterization, and transfection abilities of the green fluorescence protein (GFP) plasmid DNA in cancer cells in vitro. The results showed 100% encapsulation of pDNA (GFP) in LNPs of around 150 nm (N/P 5) indicating that the processes developed using SMART technology are consistent and can be utilized for commercial applications.

Veering to a Continuous Platform of Fused Deposition Modeling Based 3D Printing for Pharmaceutical Dosage Forms: Understanding the Effect of Layer Orientation on Formulation Performance.

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.

Bioprinting: A focus on improving bioink printability and cell performance based on different process parameters.

Three-dimensional (3D) bioprinting is an emerging biofabrication technique that shows great potential in the field of tissue engineering, regenerative medicine and advanced drug delivery. Despite the current advancement of bioprinting technology, it faces several obstacles such as the challenge of optimizing the printing resolution of 3D constructs while retaining cell viability before, during, and after bioprinting. Therefore, it is of great significance to fully understand factors that influence the shape fidelity of printed structures and the performance of cells encapsulated in bioinks. This review presents a comprehensive analysis of bioprinting process parameters that influence bioink printability and cell performance, including bioink properties (composition, concentration, and component ratio), printing speed and pressure, nozzle characteristics (size, length, and geometry), and crosslinking parameters (crosslinker types, concentration, and crosslinking time). Key examples are provided to analyze how these parameters could be tailored to achieve the optimal printing resolution as well as cell performance. Finally, future prospects of bioprinting technology, including correlation between process parameters and particular cell types with predefined applications, applying statistical analysis and artificial intelligence (AI)/machine learning (ML) technique in parameter screening, and optimizing four-dimensional (4D) bioprinting process parameters, are highlighted.

Using bugs as drugs: Administration of bacteria-related microbes to fight cancer.

Bioengineering of bacteria-related microbes has demonstrated a great potential in targeted cancer therapy. Presently, the major administration routes of bacteria-related microbes for cancer treatment include intravenous injection, intratumoral injection, intraperitoneal injection, and oral delivery. Routes of bacteria administration are critical since different delivery approaches might exert anticancer effects through diverse mechanisms. Herein, we provide an overview of the primary routes of bacteria administration as well as their advantages and limitations. Furthermore, we discuss that microencapsulation can overcome some of the associated challenges with the administration of free bacteria. We also review the latest advancements in combining functional particles with engineered bacteria to fight cancer, which can be coupled with conventional therapies to improve therapeutic effects. Moreover, we highlight the application prospect of emerging 3D bioprinting in cancer bacteriotherapy, which represents a new paradigm for personalized cancer treatment. Eventually, we provide insights into regulatory expectations and concerns regarding this field for the future translation from bench to clinic.

Four-Dimensional Printed Construct from Temperature-Responsive Self-Folding Feedstock for Pharmaceutical Applications with Machine Learning Modeling.

Four-dimensional (4D) printing, as a newly evolving technology to formulate drug delivery devices, displays distinctive advantages that can autonomously monitor drug release according to the actual physiological circumstances. In this work, we reported our earlier synthesized novel thermo-responsive self-folding feedstock for possible SSE-mediated 3D printing to form a 4D printed construct deploying machine learning (ML) modeling to determine its shape recovery behavior followed by its potential drug delivery applications. Therefore, in the present study, we converted our earlier synthesized temperature-responsive self-folding (both placebo and drug-loaded) feedstock into 4D printed constructs using SSE-mediated 3D printing technology. Further, the shape memory programming of the printed 4D construct was achieved at 50 °C followed by shape fixation at 4 °C. The shape recovery was achieved at 37 °C, and the obtained data were used to train and ML algorithms for batch optimization. The optimized batch showed a shape recovery ratio of 97.41. Further, the optimized batch was used for the drug delivery application using paracetamol (PCM) as a model drug. The % entrapment efficiency of the PCM-loaded 4D construct was found to be 98.11 ± 1.5%. In addition, the in vitro release of PCM from this programmed 4D printed construct confirms temperature-responsive shrinkage/swelling properties via releasing almost 100% ± 4.19 of PCM within 4.0 h. at gastric pH medium. In summary, the proposed 4D printing strategy pioneers the paradigm that can independently control drug release with respect to the actual physiological environment.

Multifunctional Three-Dimensional Printed Copper Loaded Calcium Phosphate Scaffolds for Bone Regeneration.

Bone regeneration using inorganic nanoparticles is a robust and safe approach. In this paper, copper nanoparticles (Cu NPs) loaded with calcium phosphate scaffolds were studied for their bone regeneration potential in vitro. The pneumatic extrusion method of 3D printing was employed to prepare calcium phosphate cement (CPC) and copper loaded CPC scaffolds with varying wt% of copper nanoparticles. A new aliphatic compound Kollisolv MCT 70 was used to ensure the uniform mixing of copper nanoparticles with CPC matrix. The printed scaffolds were studied for physico-chemical characterization for surface morphology, pore size, wettability, XRD, and FTIR. The copper ion release was studied in phosphate buffer saline at pH 7.4. The in vitro cell culture studies for the scaffolds were performed using human mesenchymal stem cells (hMSCs). The cell proliferation study in CPC-Cu scaffolds showed significant cell growth compared to CPC. The CPC-Cu scaffolds showed improved alkaline phosphatase activity and angiogenic potential compared to CPC. The CPC-Cu scaffolds showed significant concentration dependent antibacterial activity in Staphylococcus aureus. Overall, the CPC scaffolds loaded with 1 wt% Cu NPs showed improved activity compared to other CPC-Cu and CPC scaffolds. The results showed that copper has improved the osteogenic, angiogenic and antibacterial properties of CPC scaffolds, facilitating better bone regeneration in vitro.

Investigating the Use of Magnetic Nanoparticles As Alternative Sintering Agents in Selective Laser Sintering (SLS) 3D Printing of Oral Tablets.

Selective laser sintering (SLS) is a single-step, three-dimensional printing (3DP) process that is gaining momentum in the manufacturing of pharmaceutical dosage forms. It also offers opportunities for manufacturing various pharmaceutical dosage forms with a wide array of drug delivery systems. This research aimed to introduce carbonyl iron as a multifunctional magnetic and heat conductive ingredient for the fabrication of oral tablets containing isoniazid, a model antitubercular drug, via SLS 3DP process. Furthermore, the effects of magnetic iron particles on the drug release from the SLS printed tablets under a specially designed magnetic field was studied. Optimization of tablet quality was performed by adjusting SLS printing parameters. The independent factors studied were laser scanning speed, hatching space, and surface/chamber temperature. The responses measured were printed tablets' weight, hardness, disintegration time, and dissolution performance. It has been observed that, for the drug formulation with carbonyl iron, due to its inherent thermal conductivity, sintering tablets required relatively lower laser energy input to form the tablets of the same quality attributes as the other batches that contained no magnetic particles. Also, printed tablets with carbonyl iron released 25% more drugs under a magnetic field than those without it. It can be claimed that magnetic nanoparticles appear as an alternative conductive material to facilitate the sintering process during SLS 3DP of dosage forms.

Fabrication of Sustained-Release Dosages Using Powder-Based Three-Dimensional (3D) Printing Technology.

Three-dimensional (3D)-printed tablets prepared using powder-based printing techniques like selective laser sintering (SLS) typically disintegrate/dissolve and release the drug within a few minutes because of their inherent porous nature and loose structure. The goal of this study was to demonstrate the suitability of SLS 3DP technology for fabricating sustained-release dosages utilizing Kollidon® SR (KSR), a matrix-forming excipient composed of polyvinyl acetate and polyvinylpyrrolidone (8:2). A physical mixture (PM), comprising 10:85:5 (% w/w) of acetaminophen (ACH), KSR, and Candurin®, was sintered using a benchtop SLS 3D printer equipped with a 2.3-W 455-nm blue visible laser. After optimization of the process parameters and formulation composition, robust 3D-printed tablets were obtained as per the computer-aided design (CAD) model. Advanced solid-state characterizations by powder X-ray diffraction (PXRD) and wide-angle X-ray scattering (WAXS) confirmed that ACH remained in its native crystalline state after sintering. In addition, X-ray micro-computed tomography (micro-CT) studies revealed that the tablets contain a total porosity of 57.7% with an average pore diameter of 24.8 µm. Moreover, SEM images exhibited a morphological representation of the ACH sintered tablets' exterior surface. Furthermore, the KSR matrix 3D-printed tablets showed a sustained-release profile, releasing roughly 90% of the ACH over 12 h as opposed to a burst release from the free drug and PM. Overall, our work shows for the first time that KSR can be used as a suitable polymer matrix to create sustained-release dosage forms utilizing the digitally controllable SLS 3DP technology, showcasing an alternative technique and pharmaceutical excipient.

A Novel 3D Printing Particulate Manufacturing Technology for Encapsulation of Protein Therapeutics: Sprayed Multi Adsorbed-Droplet Reposing Technology (SMART).

Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. Herein, a novel manufacturing method has been introduced to produce protein-loaded chitosan particles with controlled size. This method is based on an additive manufacturing technology that allows for the designing and production of personalized particulate based therapeutic formulations with a precise control over the shape, size, and potentially the geometry. Sprayed multi adsorbed-droplet reposing technology (SMART) consists of the high-pressure extrusion of an ink with a well determined composition using a pneumatic 3D bioprinting approach and flash freezing the extrudate at the printing bed, optionally followed by freeze drying. In the present study, we attempted to manufacture trypsin-loaded chitosan particles using SMART. The ink and products were thoroughly characterized by dynamic light scattering, rheometer, Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red (FTIR) and Circular Dichroism (CD) spectroscopy. These characterizations confirmed the shape morphology as well as the protein integrity over the process. Further, the effect of various factors on the production were investigated. Our results showed that the concentration of the carrier, chitosan, and the lyoprotectant concentration as well as the extrusion pressure have a significant effect on the particle size. According to CD spectra, SMART ensured Trypsin's secondary structure remained intact regardless of the ink composition and pressure. However, our study revealed that the presence of 5% (w/v) lyoprotectant is essential to maintain the trypsin's proteolytic activity. This study demonstrates, for the first time, the viability of SMART as a single-step efficient process to produce biologics-based stable formulations with a precise control over the particulate morphology which can further be expanded across numerous therapeutic modalities including vaccines and cell/gene therapies.

3D bioprinted microparticles: Optimizing loading efficiency using advanced DoE technique and machine learning modeling.

Current microparticle (MP) development still strongly relies on the laborious trial-and-error approach. Herein, we developed a systemic method to evaluate the significance of MP formulation factors and predict drug loading efficiency (DLE) using design of experiment (DoE) and machine learning modeling. A first-in-class 3D printing concept was initially employed to fabricate polymeric MPs by a 3D printer. Sprayed Multi Adsorbed-droplet Reposing Technology (SMART) was developed to combine extrusion-based printing with emulsion evaporation technique to fabricate a small molecule drug i.e., 6-thioguanine (6-TG) loaded poly (lactide-co-glycolide) (PLGA) MPs. Compared to conventional emulsion evaporation method, SMART employs the shear force exerted by the printing nozzle rather than the sonication energy to generate smaller emulsion droplets in a single step. Furthermore, the applied shear force in the 3D printing process reported herein is controllable since the emulsion is extruded through the nozzle under preset printing conditions. The formulated MPs exhibited spherical structure with size distribution âˆ¼ 1-3µ m in diameter and reached âˆ¼ 100 % drug release at 10 h. Also, the papain-like protease (PLpro) inhibition efficacy of 6-TG in formulated MPs was maintained even after the printing process under different printing conditions. Furthermore, the formulation factor importance was assessed by DoE statistical analysis and further validated by machine learning modeling. Among the four process parameters (drug amount, printing speed, printing pressure, and nozzle size), drug amount was the most influential formulation factor. Moreover, it is interesting that nearly all the machine learning models, especially decision tree (DT), demonstrated superior performance in predicting DLE compared to DoE regression models. Overall, incorporating DoE and machine learning modeling shows great promises in the prediction and optimization of MP formulations factors by means of a novel SMART technology. Moreover, this systemic approach helps streamline the development of MP with programmable pharmaceutical attributes, representing a new paradigm for digital pharmaceutical science.

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition.

3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques.

A global bibliometric and visualized analysis of bacteria-mediated cancer therapy.

Bacteriotherapy has proved to be a powerful tool to fight against cancer. Herein, we used VOSviewer, CiteSpace, and Python to perform the first global bibliometric analysis of the literature from 2012 to 2021 on bacteria-mediated cancer therapy. Based on the results, East Asia and North America contributed the most publications to this research area. Additionally, the keyword analysis indicated that immunotherapy and nanoparticle (NP)-based drug delivery systems have long been popular topics in cancer bacteriotherapy, whereas the gut microbiota and probiotics are emerging research hotspots. This study provides crucial insights into the historical development of bacteria-mediated cancer therapy from 2012 to 2021, which will be helpful for scientists to conduct further investigation into this promising field.

Detecting Crystallinity Using Terahertz Spectroscopy in 3D Printed Amorphous Solid Dispersions.

This study demonstrates the applicability of terahertz time-domain spectroscopy (THz-TDS) in evaluating the solid-state of the drug in selective laser sintering-based 3D printed dosage forms. Selective laser sintering is a powder bed-based 3D printing platform, which has recently demonstrated applicability in manufacturing amorphous solid dispersions (ASDs) through a layer-by-layer fusion process. When formulating ASDs, it is critical to confirm the final solid state of the drug as residual crystallinity can alter the performance of the formulation. Moreover, SLS 3D printing does not involve the mixing of the components during the process, which can lead to partially amorphous systems causing reproducibility and storage stability problems along with possibilities of unwanted polymorphism. In this study, a previously investigated SLS 3D printed ASD was characterized using THz-TDS and compared with traditionally used solid-state characterization techniques, including differential scanning calorimetry (DSC) and powder X-ray diffractometry (pXRD). THz-TDS provided deeper insights into the solid state of the dosage forms and their properties. Moreover, THz-TDS was able to detect residual crystallinity in granules prepared using twin-screw granulation for the 3D printing process, which was undetectable by the DSC and XRD. THz-TDS can prove to be a useful tool in gaining deeper insights into the solid-state properties and further aid in predicting the stability of amorphous solid dispersions.

Three-Dimensional Printing of a Container Tablet: A New Paradigm for Multi-Drug-Containing Bioactive Self-Nanoemulsifying Drug-Delivery Systems (Bio-SNEDDSs).

This research demonstrates the use of fused deposition modeling (FDM) 3D printing to control the delivery of multiple drugs containing bioactive self-nano emulsifying drug-delivery systems (SNEDDSs). Around two-thirds of the new chemical entities being introduced in the market are associated with some inherent issues, such as poor solubility and high lipophilicity. SNEDDSs provide for an innovative and easy way to develop a delivery platform for such drugs. Combining this platform with FDM 3D printing would further aid in developing new strategies for delivering poorly soluble drugs and personalized drug-delivery systems with added therapeutic benefits. This study evaluates the performance of a 3D-printed container system containing curcumin (CUR)- and lansoprazole (LNS)-loaded SNEDDS. The SNEDDS showed 50% antioxidant activity (IC50) at concentrations of around 330.1 µg/mL and 393.3 µg/mL in the DPPH and ABTS radical scavenging assay, respectively. These SNEDDSs were loaded with no degradation and leakage from the 3D-printed container. We were able to delay the release of the SNEDDS from the hollow prints while controlling the print wall thickness to achieve lag phases of 30 min and 60 min before the release from the 0.4 mm and 1 mm wall thicknesses, respectively. Combining these two innovative drug-delivery strategies demonstrates a novel option for tackling the problems associated with multi-drug delivery and delivery of drugs susceptible to degradation in, i.e., gastric pH for targeting disease conditions throughout the gastrointestinal tract (GIT). It is also envisaged that such delivery systems reported herein can be an ideal solution to deliver many challenging molecules, such as biologics, orally or near the target site in the future, thus opening a new paradigm for multi-drug-delivery systems.