3D-printed immediate release solid dosage forms: a patent evaluation of US11622940B2.

Three-dimensional (3D) printing is one of the most flexible technologies for preparing tablets, offering controlled drug release profiles. The current patent describes the preparation of immediate-release 3D-printed tablets of hydrochlorothiazide to improve disintegration and dissolution profile. The patent involves the preparation of drug-loaded filament via hot-melt extrusion and utilizing the same filaments for printing 3D-printed tablets using fused deposition modeling. The tablets were printed with different shapes and sizes by incorporating channels within the tablet spaces, termed as gaplets. The introduction of channels within the tablet design improves the disintegration and dissolution profile of the drug significantly. The morphological characteristic of 3D-printed tablets was studied by using scanning electron microscopy and revealed the presence of gaplets in the tablets.

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Thermal and mechanical performance assessment of composite (CPCM) for energy storage.

Phase change materials (PCMs) face obstacles in being widely used due to issues with heat transfer and maintaining their shape. In this research, instead of using binders, the Hexadecane (H) is melted in such a way that the capillary forces of the molten wax allow it to be impregnated into the low-density polyethylene (P) molecules and bind it together as a composite. It was found that the hot melt extrusion (HME) combines the two materials at the micro-scale, forming a phase change composite (CPCM) with various geometries that possesses superior latent heat and shape stability during phase transition. The structure can incorporate a higher percentage of PCM (60 %) using this method, which also results in lower costs. According to the thermal analysis, (H60P40) provides great thermal stability and can store a lot of energy per unit of weight. It has a high capacity of storing latent heat at 129.56 J/g and can also prevent Hexadecane leakage. Based on the mechanical properties results, hexadecane acts like plasticizer thus the addition of PCM decreases Young's modulus, stress in break, and stress at yield. This trend is observed as the PCM content increases. The high values of elongation at break also indicates the strong plasticizing properties of PCM. Based on the obtained results, the CPCMs as a potential candidate for an application in buildings for thermal regulation, reducing energy consumption, and reducing indoor temperature swing.

Development of poly (lactic-co-glycolic acid) (PLGA) based implants using hot melt extrusion (HME) for sustained release of drugs: The impacts of PLGA's material characteristics.

Hot melt extrusion (HME) processed Poly (lactic-co-glycolic acid) (PLGA) implant is one of the commercialized drug delivery products, which has solid, well-designed shape and rigid structures that afford efficient locoregional drug delivery on the spot of interest for months. In general, there are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA-based implants and concurrent drug release kinetics. The objective of this study was to investigate the impacts of PLGA's material characteristics on PLGA degradation and subsequent drug release behavior from the implants. Three model drugs (Dexamethasone, Carbamazepine, and Metformin hydrochloride) with different water solubility and property were formulated with different grades of PLGAs possessing distinct co-polymer ratios, molecular weights, end groups, and levels of residual monomer (high/ViatelTM and low/ ViatelTM Ultrapure). Physicochemical characterizations revealed that the plasticity of PLGA was inversely proportional to its molecular weight; moreover, the residual monomer could impose a plasticizing effect on PLGA, which increased its thermal plasticity and enhanced its thermal processability. Although the morphology and microstructure of the implants were affected by many factors, such as processing parameters, polymer and drug particle size and distribution, polymer properties and polymer-drug interactions, implants prepared with ViatelTM PLGA showed a smoother surface and a stronger PLGA-drug intimacy than the implants with ViatelTM Ultrapure PLGA, due to the higher plasticity of the ViatelTM PLGA. Subsequently, the implants with ViatelTM PLGA exhibited less burst release than implants with ViatelTM Ultrapure PLGA, however, their onset and progress of the lag and substantial release phases were shorter and faster than the ViatelTM Ultrapure PLGA-based implants, owing to the residual monomer accelerated the water diffusion and autocatalyzed PLGA hydrolysis. Even though the drug release profiles were also influenced by other factors, such as composition, drug properties and polymer-drug interaction, all three cases revealed that the residual monomer accelerated the swelling and degradation of PLGA and impaired the implant's integrity, which could negatively affect the subsequent drug release behavior and performance of the implants. These results provided insights to formulators on rational PLGA implant design and polymer selection.

Hot-Melt Extrusion-Based Dexamethasone-PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation.

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products.

Quality of Life and Respiratory Performance in the Laryngectomized Patient: Role of the HME Filters during Physical Activity.

Background: Permanent tracheostomy because of total laryngectomy surgery entails significant consequences for patients regarding respiratory physiopathology, such as the loss of the filtering, humidifying, and heating of air by the nose. The use of special stomal filters can provide adequate protection of the tracheal-bronchopulmonary system with a reduction in respiratory pathologies. In fact, in most cases, laryngectomy patients are first cigarette smokers who for this reason also already have respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, as reported in the literature, patients often tend to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for laryngectomy patients during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomy patients, subjected to medium-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT), which involves a sustained walk lasting six minutes, with an evaluation of heart rate, oxygen saturation, and meters traveled every 60 s; furthermore, we examined two subjective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index. Conclusions: The multidisciplinary approach of the laryngectomee patient must also take pulmonary rehabilitation into consideration. It is the task of the medical team and speech therapy support to help the patient in the correct choice of HME filters taking into account daily needs.

Improved industrial induction time-based technique for evaluating kinetic hydrate inhibitors.

Kinetic hydrate inhibitor laboratory testing before field application is one of the key priorities in the oil and gas industry. The common induction-time-based technique is often used to evaluate and screen for kinetic hydrate inhibitors (KHIs). However, the main challenge relates to the stochastic nature of hydrate nucleation observed in fresh systems, which often results in scattered data on hydrate formation with unacceptable uncertainties. A much more precise KHI evaluation method, called crystal growth inhibition (CGI), provides comprehensive insights into the inhibitory behavior of a kinetic hydrate inhibitor, including both hydrate formation and decomposition. Given that industry does not require this much information, it is not feasible to expend either much time or cash on this strategy. This study aims to provide a cost-effective technique that presents maximum data accuracy and precision with relatively little time and cost expenditure. Hence, the impact of water-hydrate memory on improving the accuracy and repeatability of the results of the induction-time-based technique (IT method) was examined. First, the concept of water-hydrate memory, which contains information about how it is created, was reviewed, and then, the factors influencing it were identified and experimentally investigated, like the heating rate of hydrate dissociation and the water-hydrate memory target temperature during heating. Finally, a procedure was developed based on the background information in the earlier sections to compare the consistency of the results, originating from the conjunction of water-hydrate memory with the IT technique. The results of replications at KHI evaluation target temperatures of 12.3-12.4°C and 11.5-11.7°C showed that more repeatable data were obtained by applying water-hydrate memory, and a more conclusive decision was made in evaluating KHI performance than with an IT method. It seems that combining the IT method with water-hydrate memory, introduced as the "HME method", can lead to more definitive evaluations of KHIs. This approach is expected to gain in popularity, even surpassing the accurate but complex and time-consuming CGI method.

QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

BACKGROUND: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. RESULTS: Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes.

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R2 = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile.

1,6-Nucleophilic Di- and Trifluoromethylation of para-Quinone Methides with Me3SiCF2H/Me3SiCF3 Facilitated by CsF/18-Crown-6.

The direct 1,6-nucleophilic difluoromethylation, trifluoromethylation, and difluoroalkylation of para-quinone methides (p-QMs) with Me3SiRf (Rf = CF2H, CF3, CF2CF3, CF2COOEt, and CF2SPh) under mild conditions are described. Although Me3SiCF2H shows lower reactivity than Me3SiCF3, it can react with p-QMs promoted by CsF/18-Crown-6 to give structurally diverse difluoromethyl products in good yields. The products can then be further converted into fluoroalkylated para-quinone methides and α-fluoroalkylated diarylmethanes.

Humidification during Invasive and Non-Invasive Ventilation: A Starting Tool Kit for Correct Setting.

The humidification process of medical gases plays a crucial role in both invasive and non-invasive ventilation, aiming to mitigate the complications arising from bronchial dryness. While passive humidification systems (HME) and active humidification systems are prevalent in routine clinical practice, there is a pressing need for further evaluation of their significance. Additionally, there is often an incomplete understanding of the operational mechanisms of these devices. The current review explores the historical evolution of gas conditioning in clinical practice, from early prototypes to contemporary active and passive humidification systems. It also discusses the physiological principles underlying humidity regulation and provides practical guidance for optimizing humidification parameters in both invasive and non-invasive ventilation modalities. The aim of this review is to elucidate the intricate interplay between temperature, humidity, and patient comfort, emphasizing the importance of individualized approaches to gas conditioning.

Liquid API feeding in pharmaceutical HME: Novel options in solid dosage manufacturing.

Hot melt extrusion (HME) is a common unit operation. It is broadly applicable in the pharmaceutical industry and can be implemented in a continuous manufacturing line. However, the conventional way of active pharmaceutical ingredient (API) feeding with a pre-blend consisting of a powdered API and a polymer does not allow the flexibility and agility to adjust the process parameters, which is generally an essential part of continuous manufacturing. In addition, this method of API feeding may result in the segregation of the individual powder components or agglomeration of highly cohesive materials, leading to an inhomogeneous API content in the extrudates, especially at low doses. In this study, the universal applicability of liquid side feeding in pharmaceutical HME was demonstrated using various APIs suspended or dissolved in water and fed as suspension or undersaturated, supersaturated, and highly concentrated solutions into anterior parts of the extruder. The extrudates were characterized in terms of their API content, residual moisture content, and solid-state of the API embedded in the polymer. The results show that a uniform API content without major deviations can be obtained via this method. Furthermore, the residual moisture content of the extrudates was low enough to have no significant influence on further processing of the final dosage form. In summary, this advanced way of feeding allows an accurate, flexible, and agile feeding of APIs, facilitating the production of personalized final dosage forms and a novel option to link the manufacturing of the drug substance and the drug product.

Impact of drug load and polymer molecular weight on the 3D microstructure of printed tablets.

This study investigates the influence of drug load and polymer molecular weight on the structure of tablets three-dimensionally (3D) printed from the binary mixture of prednisolone and hydroxypropyl methylcellulose (HPMC). Three different HPMC grades, (AFFINISOLTM HPMC HME 15LV, 90 Da (HPMC 15LV); 100LV, 180 Da (HPMC 100LV); 4M, 500 Da (HPMC 4M)), which are suitable for hot-melt extrusion (HME), were used in this study. HME was used to fabricate feedstock material, i.e., filaments, at the lowest possible extrusion temperature. Filaments of the three HPMC grades were prepared to contain 2.5, 5, 10 and 20 % (w/w) prednisolone. The thermal degradation of the filaments was studied with thermogravimetric analysis, while solid-state properties of the drug-loaded filaments were assessed with the use of X-ray powder diffraction. Prednisolone in the freshly extruded filaments was determined to be amorphous for drug loads up to 10%. It remained physically stable for at least 6 months of storage, except for the filament containing 10% drug with HPMC 15LV, where recrystallization of prednisolone was detected. Fused deposition modeling was utilized to print honeycomb-shaped tablets from the HME filaments of HPMC 15LV and 100LV. The structural characteristics of the tablets were evaluated using X-ray microcomputed tomography, specifically porosity and size of structural elements were investigated. The tablets printed from HPMC 15LV possessed in general lower total porosity and pores of smaller size than tablets printed from the HPMC 100LV. The studied drug loads were shown to have minor effect on the total porosity of the tablets, though the lower the drug load was, the higher the variance of porosity along the height of the tablet was observed. It was found that tablets printed with HPMC 15LV showed higher structural similarity with the virtually designed model than tablets printed from HPMC 100LV. These findings highlight the relevance of the drug load and polymer molecular weight on the microstructure and structural properties of 3D printed tablets.

Precise Fabrication of Ocular Inserts Using an Innovative Laser-Driven CaliCut Technology: In Vitro and in Vivo Evaluation.

Ocular inserts offer distinct advantages, including a preservative-free drug delivery system, the ability to provide tailored drug release, and ease of administration. The present research paper delves into the development of an innovative ocular insert using CaliCut technology. Complementing the hot melt extrusion (HME) process, CaliCut, an advanced technology in ocular insert development, employs precision laser gauging to achieve impeccable cutting of inserts with desired dimensions. Its intelligent control over the stretching process through auto feedback-based belt speed adjustment ensures unparalleled accuracy and consistency in dosage form manufacturing. Dry eye disease (DED) poses a significant challenge to ocular health, necessitating innovative approaches to alleviate its symptoms. In this pursuit, castor oil has emerged as a promising therapeutic agent, offering beneficial effects by increasing the thickness of the lipid layer in the tear film, thus improving tear film stability, and reducing tear evaporation. To harness these advantages, this study focuses on the development and comprehensive characterization of castor oil-based ocular inserts. Additionally, in-vivo irritancy evaluation in rabbits has been undertaken to assess the inserts' safety and biocompatibility. By harnessing the HME and CaliCut techniques in the formulation process, the study demonstrates their instrumental role in facilitating the successful development of ocular inserts.

Exploring Environmental Settings to Improve the Printability of Paroxetine-Loaded Filaments by Fused Deposition Modelling.

The successful integration of hot-melt extrusion (HME) and fused deposition modelling (FDM) depends on a better understanding of the impact of environmental conditions on the printability of formulations, since they significantly affect the properties of the raw materials, whose control is crucial to enable three-dimensional printing (3DP). Hence, the objective of this work was to investigate the correlation between the environmental settings and the properties of paroxetine (PRX)-loaded filaments, previously produced by HME, which affect printability by FDM. The influence of different drying methods of the physical mixtures (PMs) and HME-filaments (FILs) on the quality and printability of these products was also assessed. The printability of FILs was evaluated in terms of the water content, and the mechanical and thermal properties of the products. Stability studies and physicochemical, thermal, and in vitro dissolution tests were carried out on the 3D-printed tablets. Stability studies demonstrated the high ductility of the PRX loaded FILs, especially under high humidity conditions. Under low humidity storage conditions (11% RH), the FILs became stiffer and were successfully used to feed the FDM printer. Water removal was slow when carried out passively in a controlled atmosphere (desiccator) or accelerated by using active drying methods (heat or microwave). Pre-drying of the PRX/excipients and/or PMs did not show any positive effect on the printability of the FIL. On the contrary, dry heat and, preferably, microwave mediated drying processes were shown to reduce the holding time required for successful FDM printing, enabling on-demand production at the point of care.

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway.

Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.

Development of Diclofenac Sodium 3D Printed Cylindrical and Tubular-Shaped Tablets through Hot Melt Extrusion and Fused Deposition Modelling Techniques.

The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME). Their formulation included DS as active substance, polyvinyl alcohol (PVA) as a polymer, different types of plasticisers (mannitol, erythritol, isomalt, maltodextrin and PEG) and superdisintegrants (crospovidone and croscarmellose sodium). The physicochemical and mechanical properties of the extruded filaments were investigated through differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile measurements. In addition, cylindrical-shaped and tubular-shaped 3D dosage forms were printed, and their dissolution behaviour was assessed via various drug release kinetic models. DSC and XRD results demonstrated the amorphous dispersion of DS into the polymeric filaments. Moreover, the 3D printed tablets, regardless of their composition, exhibited a DS release of nearly 90% after 45 min at pH 6.8, while their release behaviour was effectively described by the Korsmeyer-Peppas model. Notably, the novel tube design, which was anticipated to increase the drug release rate, proved the opposite based on the in vitro dissolution study results. Additionally, the use of crospovidone increased DS release rate, whereas croscarmellose sodium decreased it.

[Thermal imaging and velocity measurements of the exhaled airflow in total laryngectomized patients during COVID-19 pandemic.] / Különbözo védoeszközök hokamerás vizsgálata és a kilélegzett levego sebességének mérése teljes gégeeltávolításon átesett betegekben COVID­19-pandémia idején.

INTRODUCTION: In patients after total laryngectomies, the trachea and the lung can be easily infected by SARS-CoV-2 because the respiration happens through the tracheostoma. OBJECTIVE: The aim of our study was to examine whether patients with LaryTube™ can distribute aerosols to a greater extent than without LaryTube™, and to observe whether the surface of different protective instruments can be examined using the thermal camera in total laryngectomees. An important objective was also to confirm the assumption that the use of HME (heat and moisture exchanger) alone does not provide protection during COVID-19 pandemic. Finally, during our tests, we tried to get an answer to our assumption that the sample taken from the inner surface of the HME can be tested for SARS-CoV-2. METHOD: A total of 23 patients who underwent total laryngectomies were analyzed by velocity measurements and thermal imaging with and without HMEs and laryngeal tubes, using different types of PPEs. COVID-19 PCR testing was performed on patient tracheas and the inner surfaces of the HMEs. RESULTS: Male patients with laryngeal tubes without HMEs demonstrated an increase in exhaled airflow velocity of more than 43% compared to male patients without laryngeal tubes; in female patients, the same value was more than 39%. Thermal imaging results confirmed that the lowest surface temperature was measured on FFP2 masks. The sent samples can be tested for SARS-CoV-2 using PCR, the presence of the virus was not detected. CONCLUSION: Laryngectomized patients without laryngeal tubes pose a lower risk for spreading viral aerosols due to the reduced velocity of the exhaled airflow caused by the absence of the tube as the narrowing factor. Patients with laryngeal tubes who undergo total laryngectomies during the COVID-19 pandemic should use HMEs with viral filter, if possible, also changing the laryngeal tubes to dermal adhesives for fitting their HMEs seems to be the best option. The surface of the used protective equipment can also be examined with thermal camera in the case of total laryngectomees. COVID-19 PCR testing of the tracheal secretion from the inner HME surfaces should become a routine in clinical practice if deemed necessary. Orv Hetil. 2023; 164(34): 1327-1336.

Heat and Moisture Exchanger Occlusion Leading to Sudden Increased Airway Pressure: A Case Report Using ChatGPT as a Personal Writing Assistant.

Heat and moisture exchangers (HMEs) are commonly used during general anesthesia to provide appropriate humidification and warming of inspired gases. While they play a critical role in mechanical ventilation, they can also lead to acute difficult ventilation if not correctly monitored and drained. We present a case of a 56-year-old female patient who underwent lower extremity vascular bypass surgery under general anesthesia and experienced sudden increased airway pressures due to occlusion of the HME caused by excessive moisture accumulation. Proper monitoring and management of the airway circuit and HMEs can help prevent complications and ensure proper ventilation during surgery. When acute difficult ventilation is encountered during general anesthesia, a systematic approach should be taken to differentiate between patient and external factors. Other differential diagnoses for acute difficult ventilation include bronchospasm, aspiration, endotracheal tube misplacement, pulmonary embolism, and tension pneumothorax. HME occlusion should be considered as part of the differential diagnosis for intraoperative hypoxia. Proactive replacement of HMEs in long cases can prevent occlusion and ensure proper ventilation.

XRT for visualizing microstructure of extruded meat replacers.

X-Ray Tomography (XRT) was used to visualize the microstructure of extruded meat replacers. The high moisture extrudates contained lamella, that became visible upon pulling the extrudate apart. In frozen state, these lamella could be visualized with XRT. The freezing increased the density difference between the water-rich and protein-rich layers, thus increasing the contrast obtained in the XRT. Differences in the physical structure were reflected in the measured structure. In non-frozen samples, no lamella were visible, indicating insufficient contrast. Because of the contrast obtained in frozen samples, we conclude that the XRT technique is a valuable addition to investigate extrudate structure, that can be used to quantify differences in extrudates obtained by for example variation in composition. Here we showed a higher lamella thickness for soy protein isolate (SPI) compared to more fibre-rich soy protein samples.

The applications of machine learning to predict the forming of chemically stable amorphous solid dispersions prepared by hot-melt extrusion.

Amorphous solid dispersion (ASD) is one of the most important strategies to improve the solubility and dissolution rate of poorly water-soluble drugs. As a widely used technique to prepare ASDs, hot-melt extrusion (HME) provides various benefits, including a solvent-free process, continuous manufacturing, and efficient mixing compared to solvent-based methods, such as spray drying. Energy input, consisting of thermal and specific mechanical energy, should be carefully controlled during the HME process to prevent chemical degradation and residual crystallinity. However, a conventional ASD development process uses a trial-and-error approach, which is laborious and time-consuming. In this study, we have successfully built multiple machine learning (ML) models to predict the amorphization of crystalline drug formulations and the chemical stability of subsequent ASDs prepared by the HME process. We utilized 760 formulations containing 49 active pharmaceutical ingredients (APIs) and multiple types of excipients. By evaluating the built ML models, we found that ECFP-LightGBM was the best model to predict amorphization with an accuracy of 92.8%. Furthermore, ECFP-XGBoost was the best in estimating chemical stability with an accuracy of 96.0%. In addition, the feature importance analyses based on SHapley Additive exPlanations (SHAP) and information gain (IG) revealed that several processing parameters and material attributes (i.e., drug loading, polymer ratio, drug's Extended-connectivity fingerprints (ECFP) fingerprints, and polymer's properties) are critical for achieving accurate predictions for the selected models. Moreover, important API's substructures related to amorphization and chemical stability were determined, and the results are largely consistent with the literature. In conclusion, we established the ML models to predict formation of chemically stable ASDs and identify the critical attributes during HME processing. Importantly, the developed ML methodology has the potential to facilitate the product development of ASDs manufactured by HME with a much reduced human workload.