Pitfalls at Chemistry of Adenoviral Vector Vaccine against COVID-19 and how to Circumvent It.

ChAdOx1 nCoV-19 vaccine is an adenovirus vector vaccine that designed to provoke immunity against SARS-CoV-2.This vaccine contains several inactive ingredients, including sodium chloride, magnesium chloride hexahydrate, ethanol, sucrose, and Ethylenediaminetetraacetic acid (EDTA).EDTA is a very potent zinc chelator which is used commonly in protein interaction studies. Exposure to EDTA even in lower concentrations may cause extreme stripping of zinc from many proteins, in-cluding zinc-binding proteins that described as a component of the largest and most complex gene superfamily in metazoans and the most common class of transcription factors.the EDTA-induced thrombocytopenia is a risk phenomenon caused by EDTA-dependent anti-platelet auto-antibodies that identify antigens modified by EDTA.Another issue is the adenovirus in the vaccine. It can induce thrombocytopenia, a potentially serious complication of gene therapy protocols using this type of vector.PEGylation already induced significantly lower serum il-6 levels by 70% (14)We noted that the study by Katie et al studied immune response by a single dose of ChAdOx1 nCov-19 not included test of Il-6 (15)We conclude from previous studies that the PEGylating of adenoviral vectors can be promise tech-nology as safety profile as significantly reduced IL-6 and liver toxicity and how avoiding the pitfalls of chemistry and virology so the PEGylation since first time at 1999 introduced by O’Riordan,C.R et al (16) need more advancements

Antibiotic Use in Broiler Poultry Farms in Kathmandu Valley of Nepal: Which Antibiotics and Why?

Inappropriate antibiotic use in food-producing animals is associated with the emergence and spread of antibiotic resistance. In industrial broiler poultry farms in three districts of Kathmandu valley, Nepal, we assessed antibiotic use prevalence, and their classes, types, and quantities. A cross-sectional questionnaire study involving field visits to large poultry farms (flock size ≥ 3000) of the Kathmandu, Bhaktapur, and Lalitpur districts was conducted. Of 30 farms (total flock size 104,200; range 3000–6000), prevalence of antibiotic use was 90% (95% CI: 73–98%). Six (22%) farms used antibiotics as prophylaxis, while 21 (78%) used it for therapeutics. Seven antibiotics from six classes (including quinolones, macrolides, and polymyxins) were used. The most commonly used antibiotics were tylosin (47%), colistin (47%), and dual therapies with neomycin and doxycycline (33%). A total of 50,000 grams of antibiotics (total weight including active and inactive ingredients) were used (0.5 grams/chicken/45 days of flock life) with eight (26%) farms using more than two antibiotics. No farms had records on clinical indications for prophylaxis or treatment. No post-mortem records of sick birds were available. Prevalence of antibiotic use in broiler farms of Kathmandu valley is high and includes “highest priority critically important antibiotics” for human use, with direct implications on public health.

Categorization of Marketed Artificial Tear Formulations Based on Their Ingredients: A Rational Approach for Their Use

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and preservatives. The currently marketed artificial tears can be grouped into four categories based on their active ingredients. The artificial tears also contain biologically active chemicals listed as inactive ingredients, which have osmoprotectant, humectant, and tear film lipid layer or mucous layer mimicking properties. Most artificial tears contain vanishing type preservatives such as purite or sodium perborate and safer quaternary compound polyquaternium-1. The majority of these artificial tear formulations are also available as preservative-free single dose unit. The study provides a formulary of artificial tears based on active ingredients, biologically active excipients, and the preservative-free option. The formulary should assist healthcare providers in making a stepwise and rational selection of appropriate artificial tears for patients suffering from dry eye disease.

Novel RP-HPLC-PDA Approach for Efficient Simultaneous Quantification of Imipenem, Cilastatin and Relebactum in Bulk Drug and Injection Dose Forms

In this investigation, a highly reliable, precise, stability indicating, specific and selective RP-HPLC approach with photodiode array detection (RP-HPLC-PDA) was established to determine simultaneously imipenem, cilastatin and relebactum in bulk drug and injection dose forms. Chromatographic separation of imipenem, cilastatin and relebactum was achieved via using C18 XTerra column and a mobile phase poised of acetonitrile and 0.1 M dipotassium hydrogen phosphate buffer (4.5 pH, set with 0.1% orthophosphoric acid) at 45:55 (v/v) ratio with a flow stream of 1 mL/min. The photodiode array detector was fixed at wavelength 245 nm and quantifications of imipenem, cilastatin and relebactum were based on assessing their peak response areas. Good linearity was detected in target range concentrations of 250-750 μg/mL (imipenem and cilastatin) and 125-375 μg/mL (relebactum). The precision (standard variation percentage) was between 0.141% and 0.257%. Accuracy (%assay nominal) determined was between 99.144% and 99.638%. The validated RP-HPLC approach was applied to Recarbio injection dose evaluating imipenem, cilastatin and relebactum content with no interference encountered from the injection dose inactive ingredients. Imipenem, cilastatin and relebactum were subjected to forced conditions like 30% peroxide, 0.1 N NaOH, sunlight, 0.1 N HCl and 60 ºC. Imipenem, cilastatin and relebactum were effectively separated, quantified and resolved from the degradants generated in forced conditions.

Alcohol-Based Hand Sanitizers in COVID-19 Prevention: A Multidimensional Perspective

The global use of alcohol-based hand sanitizers (ABHS) as an important means of controlling the transmission of infectious disease has increased significantly as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. This paper discusses the interplay between ABHS input (formulation) factors and output (product performance) factors in the context of a multidimensional perspective using a novel representative paradigm. In the model, represented in the form of a three-dimensional tetrahedron, each of the faces represents inputs in the manufacturing of the ABHS product, which are the type and amount of alcohol, the inactive ingredients, the formulation and the manufacturing practices. The four corners of the tetrahedron represent the product performance factors which include product efficacy, sensory characteristics, usage and compliance and product safety. The multidimensional approach to the formulation and evaluation of ABHS shows that several factors contribute to the effectiveness and utility of these products. The paradigm provides a useful framework for manufacturers of ABHS and related healthcare products.

Evolution of Internal Stress in Heterogeneous Electrode Composite during the Drying Process

The mechanical behavior of electrode composite during the drying preparation has played a crucial role in the electrochemical performance of lithium-ion batteries (LIBs). Our work aimed at developing an integrated analysis method to study the component distribution, mechanical properties, and internal stress of composite coating in the process of electrode drying. The main influence factors of drying stress were thoroughly investigated. It was found that this present model could capture not only the heterogeneity effect of inactive ingredients but also the porosity-dependent viscoelasticity of electrode composite. Meanwhile, the calculated effective modulus and stress evolution upon drying time were in acceptable accord with the experimental data. Furthermore, the rapid solidification markedly increased the drying stress in electrodes and significantly impaired the tensile strength of electrode composite due to the highly gradient distributed constituents. However, the stress level at high drying temperature could be significantly reduced by an aqueous sodium alginate binder instead of poly(vinylidene fluoride). The obtained results will be a great help in efficiently manufacturing LIB electrodes with adequate mechanical integrity.

Development and validation of an HPLC method for five gliptins in pharmaceutical dosage forms in finished marketed products

Background:: Metformin is the most used antihyperglycemic drug in diabetes, and therefore it is preferred to be combined with other classes of antihyperglycemic drugs, specially gliptins. Formulating of these two classes of drug in one pharmaceutical dosage form would be more efficacious to control hyperglycemia than having either drug alone. Objective:: This study was designed and performed to develop a new, simple, and reliable method of analysis for assaying simultaneously five types of gliptins (Alogliptin, Linagliptin, Saxagliptin, Sitagliptin and Vildagliptin) and Metformin which has not been documented before. Methods:: The present method was carried out using a C18 column (250x4.6 mm), 5μm particle size, mobile phase consisting of water to acetonitrile ratio 85:15% (v/v) and the pH was set by orthophosphoric acid at 3, 10 μl injection volume, 0.5 ml flow rate, 25oC temperature and the eluent was monitored at 232 nm. Results:: The selectivity of the assay showed no interference with inactive ingredients in the formulation, and the %recovery from each drug dosage forms at three different concentrations were within the acceptable limits of the ICH guidelines. Although the method showed robustness towards flow rate, it showed significant change at 230 or 234 nm. Conclusion: The present analytical method is comprehensive and universal for measuring the five drugs and Metformin. Such an analytical method can be applied to the present available combined drug dosage forms of Metformin and one type of gliptins and the possible future of triple combinations of two gliptins and Metformin.

Alcohol-Based Hand Sanitizers – A Multidimensional Perspective

The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.