Powder Coating for Pharmaceutical Solid Dosage Forms

During the past 50 years, pharmaceutical coating has gone through the transition from sugar coating to organic solvent coating and aqueous coating. Since the 1990s, aqueous coating has largely phased out organic solvent coating as the dominate coating method for pharmaceutical dosage forms due to the toxicity and environmental related concerns caused by the organic solvents. On the other hand, although prevailing, aqueous coating has other major limitations such as higher energy consumption and longer processing time than the solvent coating. Powder coating has the benefits of both, being environmentally friendly, energy efficient and short processing time, while equally effective in modifying drug release profiles. Consequently, powder coating is pointing to the future as the next breakthrough in pharmaceutical coating. Involving three steps including preheating of the dosage forms, electrostatic deposition of coating powders and film formation (curing), powder coating has been studied to tablet coating with easily coated polymers. The objectives of the present study are to expand powder coating to more difficult coating materials such as ethylcellulose and cellulose acetate, as well as more difficult dosage forms including small pellets, and in particular, osmotic controlled release tablets. As a water-insoluble polymer, ethylcellulose (EC) is a commonly used coating material for sustained drug release. However, it is very difficult to coat by powder coating due to its high glass transition temperature (Tg). The present study was successful to coat tablets with fine particles of EC in a rotatable pan coater. With the proper addition of plasticizers, a continuous and uniform coating film was formed. Pore forming agent was added in the coating formulation to adjust the permeability of the coating film to allow a more controlled drug release rate. Currently, small pellets are coated by solvent coating or aqueous coating in a fluidized bed with a larger amount of fluidizing hot air than a pan coater, leading to an extremely high energy consumption. The present study utilized the pan coater instead of a fluidized bed to coat small pellets with powder coating, leading to a significant energy savings by avoiding the use of large amount of fluidizing hot air required to fluidize those pellets and to evaporate the organic solvent or water. Three different coating formulations containing Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were developed to achieve immediate release, sustained release and delayed release, respectively. Particularly, as the only oral drug delivery system capable of achieving constant drug release rate, osmotic drug delivery system (ODDS) is considered as the ultimate ideal drug delivery system. However, only organic solvent coating can be currently used to coat ODDS due to the high Tg of the coating materials. The present study successfully applied powder coating to coat ODDS with cellulose acetate (CA), resulting in a continuous, uniform and functionally acceptable coating film. Both elementary and porosity ODDS were achieved by using this powder coating. Following zero order drug release kinetics, drug release rate from powder coated ODDS varied with different coating levels while was independent with other factors such as drug delivery orifice diameter, pH vale of the release media and agitation speed. Considering that ODDS is the most promising controlled drug release system, the success of powder coating ODDS is a big breakthrough in pharma coating. To fully illustrate the powder coating process, in-depth characterization was carried out to investigate the coating powder deposition and film formation, and their influence factors. Positively related to the coating efficiency, powder deposition was found to be the key of the whole process, which can be promoted by preheating the dosage forms, spraying suitable liquid plasticizer and applying electrostatics for the powder spray. A curing step is necessary after coating powder adhesion to allow deposited particles to coalesce and form a continuous coating film. Finer coating powders, higher curing temperature and longer curing time would lead to a more uniform and smoother coating film

(E)-4-(2-Chloro­benzyl­ideneamino)-3-(2-chloro­phen­yl)-1H-1,2,4-triazole-5(4H)-thione–(E)-1,5-bis­(2-chloro­benzyl­idene)thio­carbonohydrazide–methanol (1/1/1)

In the title compound, C15H12Cl2N4S·C15H10Cl2N4S·C2H6O, the two chloro­phenyl rings of the triazole derivative form dihedral angles of 65.7 (2) and 44.2 (2)° with the triazole ring. In the thio­carbonohydrazide derivative, the dihedral angle between the two chloro­phenyl rings is 5.4 (2)°. In the crystal, the triazole, thio­carbonohydrazide and methanol mol­ecules are linked by N—H⋯O, N—H⋯S and O—H⋯S hydrogen bonds, forming a hexa­meric unit

Emerging Approaches to Understanding Microvascular Endothelial Heterogeneity: A Roadmap for Developing Anti-Inflammatory Therapeutics

The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium

Analysis on the Effect of Slideway Friction to the Slider-Type Hydraulic Powered Support

This paper presents a design concept of the slider-type hydraulic powered support. The equivalent mechanical model is established when the hydraulic powered support supporting the stable roof pressure and deriving the numerical calculation formula of the supporting efficiency is based on the slideway frictional coefficient. Meanwhile, theoretical solutions of supporting efficiency at different working heights are obtained. On this basis, the rigid-flexible coupling simulation model of the support was established by using Hypermesh and Adams and the dynamic simulation was carried out under the condition that the roof is bearing the stable pressure, and finally, obtaining the force response curves and the simulation solutions of the supporting efficiency. The final analysis shows the following: The slider-type powered support is suitable for working at high position; with the increase of the friction coefficient between the slider and the slideway, the supporting efficiency increases gradually, the working safety and reliability are enhanced, furthermore, its shock resistance and stability are enhanced

Microbial electrochemical enhanced composting of sludge and kitchen waste: electricity generation, composting efficiency and health risk assessment for land use

To realize the energy and resource utilization from organic solid waste, a two-phase microbial desalination cell (TPMDC) was constructed using dewatered sludge and kitchen waste as the anode substrate. The performance of electricity generation and composting efficacy was investigated, along with a comprehensive assessment of the potential health risks associated with the land use of the resulting mixed compost products. Experimental outcomes revealed a maximum open-circuit voltage of 0.893 ± 0.005 V and a maximum volumetric power density of 0.797 ± 0.009 W/m³. After 90 days of composting enhanced by microbial electrochemistry, a significant organic matter removal rate of 31.13 ± 0.44 % was obtained, and the anode substrate electric conductivity was reduced by 30.02 ± 0.04 % based on the anode desalination. Simultaneously, there was an increase in the content of available nitrogen, phosphorus, and potassium, as well as an improvement in the seed germination index. The forms of heavy metals shifted from bioavailable to stable residual states. The non-carcinogenic hazard index (HI) values for heavy metals and polycyclic aromatic hydrocarbons (PAHs) during the land use of compost products were less than 1, and the total carcinogenic risk (TCR) values for heavy metals and PAHs were below the acceptable threshold of 10−4. The occupational population risk of infection from five pathogens was higher than that of the general public, with all risk values ranging from 8.67 × 10−8 to 1, where the highest risk was attributed to occupational exposure to Legionella. These outcomes demonstrated that the mixture of dewatered sludge and kitchen waste was an appropriate anode substrate to enhance TPMDC stability for electricity generation, and its compost products have promising land use suitability and acceptable land use risk, which will provide important guidance for the safe treatment and disposal of organic solid waste.The authors gratefully acknowledge funding from Project 52270122 and 51608155 supported by National Nature Science Foundation of China, Project LH2021E097 supported by the Natural Science Foundation of Heilongjiang Province, Project QMPT-2007 supported by Harbin Medical University, support of China Scholarship Council.Heliyo

A novel hybrid machine learning model for auxiliary diagnosing myocardial ischemia

IntroductionAccurate identification of the myocardial texture features of fat around the coronary artery on coronary computed tomography angiography (CCTA) images are crucial to improve clinical diagnostic efficiency of myocardial ischemia (MI). However, current coronary CT examination is difficult to recognize and segment the MI characteristics accurately during earlier period of inflammation.Materials and methodsWe proposed a random forest model to automatically segment myocardium and extract peripheral fat features. This hybrid machine learning (HML) model is integrated by CCTA images and clinical data. A total of 1,316 radiomics features were extracted from CCTA images. To further obtain the features that contribute the most to the diagnostic model, dimensionality reduction was applied to filter features to three: LNS, GFE, and WLGM. Moreover, statistical hypothesis tests were applied to improve the ability of discriminating and screening clinical features between the ischemic and non-ischemic groups.ResultsBy comparing the accuracy, recall, specificity and AUC of the three models, it can be found that HML had the best performance, with the value of 0.848, 0.762, 0.704 and 0.729.ConclusionIn sum, this study demonstrates that ML-based radiomics model showed good predictive value in MI, and offer an enhanced tool for predicting prognosis with greater accuracy

Effects of cage vs. net-floor mixed rearing system on goose spleen histomorphology and gene expression profiles

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p < 0.05). Histological observations showed that for SW and LD, the splenic corpuscle diameter and area as well as trabecular artery diameter were larger under MRS than under CRS at 30 or 43 weeks of age (p < 0.05), while the splenic red pulp area of GE was larger under CRS than under MRS at 43 weeks of age (p < 0.05). Besides, at 43 weeks of age, higher mRNA expression levels of NGF, SPI1, and VEGFA in spleens of SW were observed under MRS than under CRS (p < 0.05), while higher levels of HSPA2 and NGF in spleens of LD were observed under MRS than under CRS (p < 0.05). For GE, there were higher mRNA expression levels of MYD88 in spleens under CRS at 30 weeks of age (p < 0.05). Moreover, our correlation analysis showed that there appeared to be more pronounced positive associations between the splenic histological parameters and expression levels of several key immune-related genes under MRS than under CRS. Therefore, it is speculated that the geese reared under MRS might exhibit enhanced immune functions than those under CRS, particularly for SW and LD. Although these phenotypic differences are assumed to be associated with the age-dependent differential expression profiles of HSPA2, MYD88, NGF, SPI1, and VEGFA in the goose spleen, the underlying regulatory mechanisms await further investigations

Investigation on the Plasma-Induced Emission Properties of Large Area Carbon Nanotube Array Cathodes with Different Morphologies

Large area well-aligned carbon nanotube (CNT) arrays with different morphologies were synthesized by using a chemical vapor deposition. The plasma-induced emission properties of CNT array cathodes with different morphologies were investigated. The ratio of CNT height to CNT-to-CNT distance has considerable effects on their plasma-induced emission properties. As the ratio increases, emission currents of CNT array cathodes decrease due to screening effects. Under the pulse electric field of about 6 V/μm, high-intensity electron beams of 170–180 A/cm2 were emitted from the surface plasma. The production mechanism of the high-intensity electron beams emitted from the CNT arrays was plasma-induced emission. Moreover, the distribution of the electron beams was in situ characterized by the light emission from the surface plasma

Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity

PurposeSepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics.MethodsFollowing informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1β/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA.ResultsWe identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs.ConclusionNeutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions

Safety and Immunogenicity of H5N1 Influenza Vaccine Based on Baculovirus Surface Display System of Bombyx mori

Avian influenza virus (H5N1) has caused serious infections in human beings. This virus has the potential to emerge as a pandemic threat in humans. Effective vaccines against H5N1 virus are needed. A recombinant Bombyx mori baculovirus, Bmg64HA, was constructed for the expression of HA protein of H5N1 influenza virus displaying on the viral envelope surface. The HA protein accounted for approximately 3% of the total viral proteins in silkworm pupae infected with the recombinant virus. Using a series of separation and purification methods, pure Bmgp64HA virus was isolated from these silkworm pupae bioreactors. Aluminum hydroxide adjuvant was used for an H5N1 influenza vaccine. Immunization with this vaccine at doses of 2 mg/kg and 0.67 mg/kg was carried out to induce the production of neutralizing antibodies, which protected monkeys against influenza virus infection. At these doses, the vaccine induced 1:40 antibody titers in 50% and 67% of the monkeys, respectively. The results of safety evaluation indicated that the vaccine did not cause any toxicity at the dosage as large as 3.2 mg/kg in cynomolgus monkeys and 1.6 mg/kg in mice. The results of dose safety evaluation of vaccine indicated that the safe dose of the vaccine were higher than 0.375 mg/kg in rats and 3.2 mg/kg in cynomolgus monkeys. Our work showed the vaccine may be a candidate for a highly effective, cheap, and safe influenza vaccine for use in humans