Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues. Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC). Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi. Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

[Box: see text].

3D printed benznidazole tablets based on an interpolyelectrolyte complex by melting solidification printing process (MESO-PP): An innovative strategy for personalized treatment of Chagas disease.

3D printing technology is revolutionizing pharmaceuticals, offering tailored solutions for solid dosage forms. This innovation is particularly significant for conditions like Chagas disease, which require weight-dependent treatments. In this work, a formulation of benznidazole (BNZ), the primary treatment for this infection, was developed to be utilized with the Melting Solidification Printing Process (MESO-PP) 3D printing technique. Considering the limited aqueous solubility of BNZ, an interpolyelectrolyte complex (IPEC), composed of chitosan and pectin, was integrated to improve its dissolution profile. The formulations, also called inks in this context, with and without IPEC were integrally characterized and compared. The printing process was studied, the release of BNZ from 3D-prints (3DP) was exhaustively analyzed and a physiologically based pharmacokinetic model (PKPB) was developed to forecast their pharmacokinetic performance. 3DP were successfully achieved loading 25, 50 and 100 mg of BNZ. The presence of the IPEC in the ink caused a decrease in the crystalline domain of BNZ and facilitated the printing process, reaching a print success rate of 83.3 %. Interestingly, 3DP-IPEC showed accelerated release dissolution profiles, releasing over 85 % of BNZ in 90 min, while 3DP took up to 48 h for doses above 25 mg. The PBPK model demonstrated that 3DP-IPEC tablets would present high bioavailability (0.92), higher than 3DP (0.36) and similar to the commercial product. This breakthrough holds immense potential for improving treatment outcomes for neglected diseases.

Kinetic Study of Anaerobic Adhesive Curing on Copper and Iron Base Substrates.

Anaerobic adhesives (AAs) cure at room temperature in oxygen-deprived spaces between metal substrates. The curing process is significantly influenced by the type of metal ions present. This study investigates the curing kinetics of a high-strength AA on iron and copper substrates using differential scanning calorimetry (DSC). The activation energy and kinetic parameters were determined with different empiric models, revealing that curing on copper is faster and more complete compared to iron. The findings suggest that copper ions lower the activation energy required for curing, enhancing the adhesive's performance. This research addresses the gap in understanding how metal ions affect AA curing kinetics, offering valuable insights for optimizing adhesive formulations for industrial applications.

3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

Wear Behavior of Epoxy Resin Reinforced with Ceramic Nano- and Microparticles.

Cavitation erosion poses a significant challenge in fluid systems like hydraulic turbines and ship propellers due to pulsed pressure from collapsing vapor bubbles. To combat this, various materials and surface engineering methods are employed. In this study, nano and micro scale particles of silicon carbide (SiC) or boron carbide (B4C) were incorporated as reinforcement at 6% and 12% ratios, owing to their exceptional resistance to abrasive wear and high hardness. Microparticles were incorporated to assess the damage incurred during the tests in comparison to nanoparticles. Wear tests were conducted on both bulk samples and coated aluminum sheets with a 1mm of composite. Additionally, cavitation tests were performed on coated aluminum tips until stability of mass loss was achieved. The results indicated a distinct wear behavior between the coatings and the bulk samples. Overall, wear tended to be higher for the coated samples with nanocomposites than bulk, except for the nano-composite material containing 12% SiC and pure resin. With the coatings, higher percentages of nanometric particles correlated with increased wear. The coefficient of friction remained within the range of 0.4 to 0.5 for the coatings. Regarding the accumulated erosion in the cavitation tests for 100 min, it was observed that for all nanocomposite materials, it was lower than in pure resin. Particularly, the composite with 6% B4C was slightly lower than the rest. In addition, the erosion rate was also lower for the composites.

Formulation and optimization of pH-sensitive nanocrystals for improved oral delivery.

The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp®, with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner.

Significant progress in improving Atorvastatin dissolution rate: Physicochemical characterization and stability assessment of self-dispersible Atorvastatin/Tween 80® nanocrystals formulated through wet milling and freeze-drying.

Atorvastatin (ATV) is a first-line drug for the treatment of hyperlipidemia. This drug presents biopharmaceutical problems, partly due to its low solubility and dissolution rate. In this work, nanocrystals of ATV stabilized with Tween 80® were designed by wet milling. A full factorial design was applied to optimize the process. Additionally, a cryoprotectant agent (maltodextrin, MTX) was identified, which allowed maintaining the properties of the nanocrystals after lyophilization. The storage stability of the nanocrystals was demonstrated for six months in different conditions. The obtained nanocrystal powder was characterized using SEM, EDXS, TEM, DSC, TGA, FT-IR, and XRD, showing the presence of irregular crystals with semi-amorphous characteristics, likely due to the particle collision process. Based on the reduction in particle size and the decrease in drug crystallinity, a significant increase in water and phosphate buffer (pH 6.8) solubility by 4 and 6 times, respectively, was observed. On the other hand, a noticeable increase in the dissolution rate was observed, with 90 % of the drug dissolved within 60 min of study, compared to 30 % of the drug dissolved within 12 h in the case of the untreated drug or the physical mixture of components. Based on these results, it can be concluded that the nano-milling of Atorvastatin stabilized with Tween 80® is a promising strategy for developing new formulations with improved biopharmaceutical properties of this widely used drug.

Hybridization Effect on Interlaminar Bond Strength, Flexural Properties, and Hardness of Carbon-Flax Fiber Thermoplastic Bio-Composites.

Hybridizing carbon-fiber-reinforced polymers with natural fibers could be a solution to prevent delamination and improve the out-of-plane properties of laminated composites. Delamination is one of the initial damage modes in composite laminates, attributed to relatively poor interlaminar mechanical properties, e.g., low interlaminar strength and fracture toughness. This study examined the interlaminar bond strength, flexural properties, and hardness of carbon/flax/polyamide hybrid bio-composites using peel adhesion, three-point bending, and macro-hardness tests, respectively. In this regard, interlayer hybrid laminates were produced with a sandwich fiber hybrid mode, using woven carbon fiber plies (C) as the outer layers and woven flax fiber plies (F) as the inner ones (CFFC) in combination with a bio-based thermoplastic polyamide 11 matrix. In addition, non-hybrid carbon and flax fiber composites with the same matrix were produced as reference laminates to investigate the hybridization effects. The results revealed the advantages of hybridization in terms of flexural properties, including a 212% higher modulus and a 265% higher strength compared to pure flax composites and a 34% higher failure strain compared to pure carbon composites. Additionally, the hybrid composites exhibited a positive hybridization effect in terms of peeling strength, demonstrating a 27% improvement compared to the pure carbon composites. These results provide valuable insights into the mechanical performance of woven carbon-flax hybrid bio-composites, suggesting potential applications in the automotive and construction industries.

Design of a pilot plant-type pharmaceutical reactor to address the problem of interchangeability of generic semisolid formulations.

OBJECTIVE AND SIGNIFICANCE: This research aims to design and develop a pilot plant-type pharmaceutical reactor with a strong focus on its volumetric capacity and heat transfer capabilities. The primary goal is to replicate design and control strategies at the laboratory or pilot scale to analyze and produce generic semisolid formulations. METHODS: Computational fluid dynamics and heat transfer modeling, utilizing the finite volume method, were employed to determine the reactor's performance and particle trajectory during the mixing and stirring. This allowed for the establishment of optimal operational parameters and variables. Furthermore, prototypes were constructed at 1:2.5 and 1:15 scales to examine the reactor's morphology, ensure volumetric versatility, and conduct mixing, homogenization, and coloration tests using varying volumes. RESULTS AND CONCLUSIONS: The outcomes of this study yielded a versatile reactor suitable for processing pharmaceutical semisolids at both laboratory and pilot-scale volumes. Notably, the reactor demonstrated exceptional volumetric capacity within a single vessel while effectively facilitating heat transfer to its interior.

3D-Printed Gastroretentive Tablets Loaded with Niclosamide Nanocrystals by the Melting Solidification Printing Process (MESO-PP).

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

Design and Development of Sublingual Printlets Containing Domperidone Nanocrystals Using 3D Melting Solidification Printing Process (MESO-PP).

Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose significant administration challenges. In this study, we aimed to improve DOM solubility and avoid its metabolism by developing nanocrystals (NC) of DOM through a 3D printing technology-melting solidification printing process (MESO-PP)-to be delivered via a solid dosage form (SDF) that can be administered sublingually. We obtained DOM-NCs using the wet milling process and designed an ultra-rapid release ink (composed of PEG 1500, propylene glycol, sodium starch glycolate, croscarmellose sodium, and sodium citrate) for the 3D printing process. The results demonstrated an increase in the saturation solubility of DOM in both water and simulated saliva without any physicochemical changes in the ink as observed by DSC, TGA, DRX, and FT-IR. The combination of nanotechnology and 3D printing technology enabled us to produce a rapidly disintegrating SDF with an improved drug-release profile. This study demonstrates the potential of developing sublingual dosage forms for drugs with low aqueous solubility using nanotechnology and 3D printing technology, providing a feasible solution to the challenges associated with the administration of drugs with low solubility and extensive metabolism in pharmacology.

Polymerization Kinetics of Acrylic Photopolymer Loaded with Graphene-Based Nanomaterials for Additive Manufacturing.

Graphene-based nanomaterials (GBN) can provide attractive properties to photocurable resins used in 3D printing technologies such as improved mechanical properties, electrical and thermal conductivity, and biological capabilities. However, the presence of GBN can affect the printing process (e.g., polymerization, dimensional stability, or accuracy), as well as compromising the quality of structures. In this study an acrylic photocurable resin was reinforced with GBN, using methyl methacrylate (MMA) to favor homogenous dispersion of the nanomaterials. The objective was to investigate the influence that the incorporation of GBN and MMA has on polymerization kinetics by Differential Scanning Calorimetry using Model Free Kinetics, ultra-violet (UV) and thermal triggered polymerization. It was found that MMA catalyzed polymerization reaction by increasing the chain's mobility. In the case of GBNs, graphene demonstrated to inhibit both, thermally and UV triggered polymerization, whilst graphene oxide showed a double effect: it chemically inhibited the polymerization reaction during the initialization stage, but during the propagation stage it promoted the reaction. This study demonstrated that MMA can be used to achieve photocurable nanocomposites with homogenously dispersed GBN, and that the presence of GBN significantly modified the polymerization mechanism while an adaptation of the printing parameters is necessary in order to allow the printability of these nanocomposites.

Design and production of 3D printed oral capsular devices for the modified release of urea in ruminants.

The use of 3D printing for the production of systems intended for oral delivery of diet supplements in the veterinary pharmacy constitutes an attractive technology that has remained unexplored. In this sense, this work studies the design and 3D printing of capsular devices that allow the modified release of urea, which is frequently used as a source of non-protein nitrogen in ruminants, but highly toxic if fast ingested. The devices were printed with combinations of polylactic acid (PLA, water-insoluble) and polyvinyl alcohol (PVA, water-soluble) in order to modulate the urea release through the different parts. The optimization of the designs as well as printing parameters such as extrusion temperature, printing speed, retraction distance and nozzle speed resulted critical to obtain successful capsular devices. In addition, the dissolution studies confirmed that the developed designs showed a controlled release of urea, especially the ones that presented internal partitions. Finally, Logistic and Weibull equations were the kinetic models that best fitted the experimental data corresponding to functions that describe S-shaped dissolution profiles. Overall, this work constitutes a proof of concept and provides the first steps in the development of 3D printed simple devices for the controlled release of supplements and drugs in veterinary pharmacy.

Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole.

PURPOSE: 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating systems using ricobendazole (RBZ) as a model drug and a combination of polymers were designed and obtained by melt solidification printing technique (MESO-PP). METHODS: Four different MESO-PP inks were formulated based on combinations of the polymers Gelucire 43/01 and Gelucire 50/13 in different ratios. For each of the formulated inks, physicochemical characterization was performed by thermal analysis (thermogravimetric analysis [TGA] and differential scanning calorimetry [DSC]), fourier transform infrared spectrophotometer (FTIR) and X-ray diffraction (XRD). Pharmaceutical characterization was performed by in vitro assays to determine pharmaceutically relevant parameters. These parameters were calculated by applying mathematical models developed to evaluate in vitro drug release profiles. On the other hand, a physiologically based pharmacokinetic (PBPK) model was developed to predict the in vivo performance of RBZ loaded in the different inks by determining the Cmax, and the AUC0-∞. RESULTS: By increasing the proportion of Gelucire 50/13 co-surfactant in the mixtures (the proportion in Ink 1 was 33%, while the proportion in Ink 4 was 80%), the dissolution capacity of RBZ increases substantially, decreasing flotation times. CONCLUSION: MESO-PP produced ink 1 (50% Gelucire 43/01, 25% Gelucire 50/13 and 25% RBZ), which has a zero-order release (RR = 0.180%/min) and the longest flotation time (545 ± 23 min), and in turn would produce a significant increase in oral absorption of the drug, with an AUC0-∞ 2.16-fold higher than that obtained in animals treated with RBZ loaded in conventional tablets.

Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride.

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Nanocrystal-based 3D-printed tablets: Semi-solid extrusion using melting solidification printing process (MESO-PP) for oral administration of poorly soluble drugs.

This is the first report on the inclusion of nanocrystals (NCs) within 3D-printed oral solid dosage forms -3D-printed tablets or printlets- produced by the Melting Solidification Printing Process (MESO-PP) 3D printing technique. This method allowed the incorporation of albendazole (ABZ) nanocrystals in a concentration of up to 50% w/w, something not achieved in conventional tablets. An ink of PEG 1500/propylenegycol was used as a carrier and no physicochemical interactions or crystallinity modifications were observed due to the inclusion of ABZ-NCs into the ink, as demonstrated by TGA, DSC, XRD and FT-IR. In particular, the relative crystallinity of the ink loaded with NCs was 97.8% similar to the physical mixture of the components. Moreover, the presence of NCs was observed in the surface and matrix of the printlets by SEM. In addition, the printlet NCs demonstrated to be more effective than NCs included in hard gelatin capsules in improving drug dissolution in HCl 0.1 N. The particle size, crystallinity and chemical stability of the nanocrystals was maintained before and after 180 days of storage. Thus, these findings exhibit relevant pharmaceutical potential for developing stable, fast-release, oral, solid dosage forms of poorly soluble drugs combining 3D printing and nanocrystals. Additionally, this technique could be applied for printing objects using different types of nanocrystals embedded in low melting temperature polymers.

Advanced G-MPS-PMMA Bone Cements: Influence of Graphene Silanisation on Fatigue Performance, Thermal Properties and Biocompatibility.

The incorporation of well-dispersed graphene (G) powder to polymethyl methacrylate (PMMA) bone cement has been demonstrated as a promising solution to improving its mechanical performance. However, two crucial aspects limit the effectiveness of G as a reinforcing agent: (1) the poor dispersion and (2) the lack of strong interfacial bonds between G and the matrix of the bone cement. This work reports a successful functionalisation route to promote the homogenous dispersion of G via silanisation using 3-methacryloxypropyltrimethoxy silane (MPS). Furthermore, the effects of the silanisation on the mechanical, thermal and biocompatibility properties of bone cements are presented. In comparison with unsilanised G, the incorporation of silanised G (G_MPS1 and G_MPS2) increased the bending strength by 17%, bending modulus by 15% and deflection at failure by 17%. The most impressive results were obtained for the mechanical properties under fatigue loading, where the incorporation of G_MPS doubled the Fatigue Performance Index (I) value of unsilanised G-bone cement-meaning a 900% increase over the I value of the cement without G. Additionally, to ensure that the silanisation did not have a negative influence on other fundamental properties of bone cement, it was demonstrated that the thermal properties and biocompatibility were not negatively impacted-allowing its potential clinical progression.

Nivel de conocimientos en la prevención del cáncer de próstata en derechohabientes de una unidad de medicina familiar / Level of knowledge in prostate cancer prevention in beneficiaries from a family medicine unit

Introducción: el cáncer es una de las primeras causas de muerte mundial; en 2012 representó 8.2 millones de muertes. En México, a pesar de que la incidencia de cáncer de próstata es tres veces menor que lo observado en Estados Unidos, la mortalidad por esta causa es prácticamente igual (11.3 vs 9.8 muertes por cada 100,000 hombres) y representa la primera causa de cáncer y mortalidad por cáncer en hombres, por lo que es de vital importancia la prevención y para ello se debe promover el conocimiento de esta afección. Objetivo: identificar el nivel de conocimientos sobre la prevención del cáncer de próstata en hombres de 40 a 65 años de la Unidad de Medicina Familiar No. 51. Metodología: estudio descriptivo transversal. Se aplicó un cuestionario validado (alfa de Cronbach de 0.8) sobre las medidas preventivas del cáncer prostático a 204 derechohabientes masculinos de la unidad. Resultados: el grado de conocimientos sobre la prevención del cáncer de próstata es bajo en el 66% de los casos, me- dio en el 31% y alto en el 3%; el 78.9% de los participantes corresponde a casados, el 51.5% tiene grado de estudios de preparatoria o superior y el 47.1% es obrero. Conclusiones: el bajo grado de conocimientos en la prevención del cáncer prostático muestra un área de oportunidad de mejorar si se difunde a edades tempranas.

Introduction: Cancer is one of the leading causes of death worldwide; in 2012, 8.2 million deaths were attributed to it. In Mexico, despite the fact that the incidence of prostate cancer is three times lower than that observed in the United States, mortality from this cause is practically the same (11.3 vs. 9.8 deaths per 100 000 men) and represents the first cause of cancer and cancer mortality in men, which is why prevention is of vital importance, and for this, knowledge about the pathology must be promoted. Objective: To identify the level of knowledge about the pre- vention of prostate cancer in men between 40 and 65 years from the Family Medicine Unit No. 51. Methodology: Descriptive cross-sectional study. A validated questionnaire (Cronbach's alpha of 0.8) on preventive measures of prostate cancer was applied to 204 male beneficiaries from the aforementioned unit. Results: The level of knowledge about the prevention of prostate cancer is low in 66% of the cases, medium in 31% and high in 3%; 78.9% are married, 51.5% have a high school education level or higher and 47.1% are workers. Conclusions: The low level of knowledge of prostate cancer prevention shows an area of opportunity for improvement with a greater emphasis on early ages.

Advances in Biodegradable 3D Printed Scaffolds with Carbon-Based Nanomaterials for Bone Regeneration.

Bone possesses an inherent capacity to fix itself. However, when a defect larger than a critical size appears, external solutions must be applied. Traditionally, an autograft has been the most used solution in these situations. However, it presents some issues such as donor-site morbidity. In this context, porous biodegradable scaffolds have emerged as an interesting solution. They act as external support for cell growth and degrade when the defect is repaired. For an adequate performance, these scaffolds must meet specific requirements: biocompatibility, interconnected porosity, mechanical properties and biodegradability. To obtain the required porosity, many methods have conventionally been used (e.g., electrospinning, freeze-drying and salt-leaching). However, from the development of additive manufacturing methods a promising solution for this application has been proposed since such methods allow the complete customisation and control of scaffold geometry and porosity. Furthermore, carbon-based nanomaterials present the potential to impart osteoconductivity and antimicrobial properties and reinforce the matrix from a mechanical perspective. These properties make them ideal for use as nanomaterials to improve the properties and performance of scaffolds for bone tissue engineering. This work explores the potential research opportunities and challenges of 3D printed biodegradable composite-based scaffolds containing carbon-based nanomaterials for bone tissue engineering applications.

Design of novel oral ricobendazole formulation applying melting solidification printing process (MESO-PP): An innovative solvent-free alternative method for 3D printing using a simplified concept and low temperature.

This paper describes a melting solidification printing process (MESO-PP) capable of obtaining printed oral solid dosage forms in a safe, versatile, and robust manner avoiding the use of solvents and high temperatures. MESO-PP and Gelucire® 50/13 (fatty polyethylene glycol esters) as ink can be used to obtain a floating sustained-release system with the aim of improving the dissolution and absorption of drugs, such as ricobendazole (RBZ), which have a low and erratic bioavailability. Gelucire 50/13 can be considered a good material to formulate inks using MESO-PP. As a model, the RBZ allowed us to assess that there were no changes in crystallinity and the API-ink interactions were ruled out using TGA, DSC, XRD and FT-IR assays. A batch of printlets, obtained using MESO-PP, fulfilled USP requirements regarding uniformity of mass (827 ± 9 mg) and drug content (211 ± 5 mg). Hardness and friability were 39.23 ± 9.65 N and 1.07 ± 0.5% respectively, just above the 1% USP tablet-friability limit. It was possible to obtain tablets of different sizes with high precision (r2 = 0.995). In vitro dissolution test showed that the printlet had a sustained-release of RBZ (only 7% after 15 min), that erosion was the predominant mechanism for drug release (n-value of Korsmeyer-Peppas equation = 0.991; r2 = 0.99) and that changes in the internal structures modify the release. Consequently, MESO-PP can be considered an excellent alternative to obtain solid pharmaceutical dosage forms with variable geometries for different pharmaceutical applications.