Computational Support to Explore Ternary Solid Dispersions of Challenging Drugs Using Coformer and Hydroxypropyl Cellulose.

A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e.

Cross-Sectional Study of Q Fever Seroprevalence among Blood Donors, Israel, 2021.

We evaluated Q fever prevalence in blood donors and assessed the epidemiologic features of the disease in Israel in 2021. We tested serum samples for Coxeilla burnetii phase I and II IgG using immunofluorescent assay, defining a result of >200 as seropositive. We compared geographic and demographic data.

A new type of C⋯H(C=) bond in adducts of vinyl carbocations with alkenes.

By X-ray diffraction analysis and IR spectroscopy, it was established here that vinyl carbocations CH/CH with carborane counterion CHBCl form stable monosolvates CH⋅CH/CH⋅CH with molecules of alkenes CH/CH. They contain molecular group =C⋯H-C= with a new type of bond formed by the H atom of the H-C= group of the alkene with the C atom of the C=C group of the carbocation. The short C----C distance, equal to 2.

Phase homogeneity in ternary amorphous solid dispersions and its impact on solubility, dissolution and supersaturation - Influence of processing and hydroxypropyl cellulose grade.

As performance of ternary amorphous solid dispersions (ASDs) depends on the solid-state characteristics and polymer mixing, a comprehensive understanding of synergistic interactions between the polymers in regard of dissolution enhancement of poorly soluble drugs and subsequent supersaturation stabilization is necessary. By choosing hot-melt extrusion (HME) and vacuum compression molding (VCM) as preparation techniques, we manipulated the phase behavior of ternary efavirenz (EFV) ASDs, comprising of either hydroxypropyl cellulose (HPC)-SSL or HPC-UL in combination with Eudragit® L 100-55 (EL 100-55) (50:50 polymer ratio), leading to single-phased (HME) and heterogeneous ASDs (VCM). Due to higher kinetic solid-state solubility of EFV in HPC polymers compared to EL 100-55, we visualized higher drug distribution into HPC-rich phases of the phase-separated ternary VCM ASDs via confocal Raman microscopy.

Substitution of H Atoms in Unsaturated (Vinyl-Type) Carbocations by Cl or O Atoms.

Introduction of Cl and O atoms into C-vinyl carbocations was studied by X-ray diffraction analysis and IR spectroscopy. Chlorine atoms are weak electron acceptors in ordinary molecules but, within vinyl carbocations, manifest themselves as strong electron donors that accept a positive charge. The attachment of a Cl atom directly to a C=C bond leads to an increase in the e-density on it, exceeding that of the common double bond.

Tailored ASD destabilization - Balancing shelf life stability and dissolution performance with hydroxypropyl cellulose.

Amorphous solid dispersion (ASD) formulations are preferred enabling formulations for poorly water soluble active pharmaceutical ingredients (API) as they reliably enhance the dissolution behavior and solubility. Balancing a high stability against unwanted transformations such as crystallization and amorphous phase separation during storage on the one hand and optimizing the dissolution behavior of the formulation (high supersaturation and maintenance for long time) on the other hand are essential during formulation development. This study assessed the potential of ternary ASDs (one API and two polymers) ntaining the polymers hydroxypropyl cellulose together with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) or hydroxypropyl cellulose acetate succinate to stabilize the amorphously embedded APIs fenofibrate and simvastatin during storage and to enhance the dissolution performance.

Linking between ambient pollution and metals concentration in blood. Nationwide study based on the national blood banking system.

This study was aimed to describe the chemical traces of air pollution in blood of residents and evaluate the association between ambient pollution and its dose absorbed internally by a human body. The national Magen David Adom Blood Services blood donation collection platform and the National Public Health Laboratory's testing services were utilized to conduct a human biomonitoring study among blood donors in Israel. The donors' residential addresses and donations sites' locations were geocoded and merged with the levels of pollutants recorded by the nearby monitoring stations.

Predictors of reinfection with pre-Omicron and Omicron variants of concern among individuals who recovered from COVID-19 in the first year of the pandemic.

Objectives: The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals.

Methods: Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection.

National blood bank services as a platform for national human biomonitoring - A proof-of-concept study.

Background: Human biomonitoring (HBM) is crucial for identifying potential risks to human health from exposure to environmental hazards. However, it is an expensive and labor-intensive endeavor. To save on samples' collection process we suggested using a national blood banking system as a platform for a national HBM program.

Physiological Buffer Effects in Drug Supersaturation - A Mechanistic Study of Hydroxypropyl Cellulose as Precipitation Inhibitor.

Phosphate buffer is predominantly used instead of the more physiological bicarbonate buffer, as the latter requires a technical solution of adequate gas mixing. Recent pioneering work on how bicarbonate buffer affected drug supersaturation revealed interesting effects that call for more mechanistic understanding. Therefore, this study used hydroxypropyl cellulose as a model precipitation inhibitor and real-time desupersaturation testing was conducted with the drugs bifonazole, ezetimibe, tolfenamic acid and triclabendazole.

Interaction of Vinyl-Type Carbocations, CH and CH with Molecules of Water, Alcohols, and Acetone.

X-ray diffraction analysis and IR spectroscopy were used to study the products of the interaction of vinyl cations CH and CH (Cat) (as salts of carborane anion CHBCl) with basic molecules of water, alcohols, and acetone that can crystallize from solutions in dichloromethane and CHF. Interaction with water, as content increased, proceeded via three-stages. (1) adduct Cat·OH forms in which HO binds (through the O atom) to the C=C bond of the cation with the same strength as seen in the binding to Na in Na(HO).

Spontaneous Transition of Alkyl Carbocations to Unsaturated Vinyl-Type Carbocations in Organic Solutions.

It was found that alkyl carbocations, when their salts are dissolved in common organochlorine solvents, decompose to unsaturated vinyl-type carbocations that are stabler in solutions. This is a convenient method for obtaining salts of vinyl cations and their solutions for further research.

The Chloronium Cation [(CH)Cl] and Unsaturated C-Carbocations with C=C and C≡C Bonds in Their Solid Salts and in Solutions: An H/C NMR and Infrared Spectroscopic Study.

Solid salts of the divinyl chloronium (CH)Cl cation () and unsaturated CHCl and CH carbocations with the highly stable CHBHal anion (Hal=F, Cl) were obtained for the first time. At 120 °C, the salt of the chloronium cation decomposes, yielding a salt of the CH cation. This thermally stable (up to 200 °C) carbocation is methyl propargyl, CH≡C-C-H-CH (), which, according to quantum chemical calculations, should be energetically much less favorable than other isomers of the CH cations.

IR-Spectroscopic and X-ray-Structural Study of Vinyl-Type Carbocations in Their Carborane Salts.

The butylene carbocation in its salts with anions CHBF and CHBCl forms isomers CH=C-CH-CH () and CH-C=CH-CH (), which were characterized here by infrared (IR) spectroscopy and X-ray diffraction analysis. The strongest influence on the structure of the cations is exerted by geometric ordering of their anionic environment. In the crystalline phase, the cations uniformly interact with neighboring anions, and the C=C bond is located in the middle part of the cations forming a -CH=C- moiety with the highest positive charge on it and the lowest νC=C frequency, at 1490 cm.

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions.

A current trend in the development of amorphous solid dispersions (ASDs) is the combination of two polymers for synergistic enhancement in supersaturation of poorly soluble drugs. We investigated the supersaturation potential of celecoxib (CXB) using combinations of methacrylic acid-ethyl acrylate copolymer (1:1) (EL 100-55) and hydroxypropyl cellulose (HPC) SSL. Initially, the supersaturation potential of single polymers and combinations in various ratios was assessed.

Hydroxypropyl Cellulose for Drug Precipitation Inhibition: From the Potential of Molecular Interactions to Performance Considering Microrheology.

There has been recent interest in using hydroxypropyl cellulose (HPC) for supersaturating drug formulations. This study investigated the potential for molecular HPC interactions with the model drug celecoxib by integrating novel approaches in the field of drug supersaturation analysis. Following an initial polymer characterization study, quantum-chemical calculations and molecular dynamics simulations were complemented with results of inverse gas chromatography and broadband diffusing wave spectroscopy.

Correlation of Anti-SARS-CoV-2 S1-specificIgG antibody levels and adverse events following vaccination with BNT162b2 mRNA COVID-19 vaccine in healthcare workers.

Currently approved anti-COVID-19 vaccines have been found to be safe and effective and almost 60% of Israeli residents are already vaccinated with BNT162b2 vaccine. This observational study was designed to evaluate the adverse events of vaccine reported by 61 healthcare workers at least 7 days after the 2nd vaccination, and to investigate the correlation of adverse events and anti-SARS-CoV-2 IgG antibody levels. The median participant's age was 51.

Isomers of the Allyl Carbocation CH in Solid Salts: Infrared Spectra and Structures.

Three isomers of the allyl cation CH were obtained in salts with the carborane anion CHBCl . Two of them, angular CH-CH=CH () and linear CH-C=CH (), were characterized by X-ray crystallography, and the third one, (CHCHCH) (), is formed in an amorphous salt. The stretch vibration of the charged double bond C=C of and is decreased by 162 cm () or 76 cm () as compared to that of neutral propene.

Unsaturated Vinyl-Type Carbocation [(CH)C=CH] in Its Carborane Salts.

The isobutylene carbocation (CH)C=CH was obtained in amorphous and crystalline salts with the carborane anion CHBCl . The cation was characterized by X-ray crystallography and IR spectroscopy. Its crystal structure shows a relatively uniform ionic interaction of the cation with the surrounding anions, with a slightly shortened distance between the C atom of the =CH group and the Cl atom of the anion, pointing to a higher positive charge on this group.

Qualifying coronavirus disease 2019 convalescent plasma donors in Israel.

Background And Objectives: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel.

Materials And Methods: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.

and assessment of hydroxypropyl cellulose as functional additive for enabling formulations containing itraconazole.

Using polymers as additives to formulate ternary amorphous solid dispersions (ASDs) has successfully been established to increase the bioavailability of poorly soluble drugs, when one polymer is not able to provide both, stabilizing the drug in the matrix and the supersaturated solution. Therefore, we investigated the influence of low-viscosity hydroxypropyl cellulose (HPC) polymers as an additive in HPMC based ternary ASD formulations made by hot-melt extrusion (HME) on the bioavailability of itraconazole (ITZ). The partitioning potential of the different HPC grades was screened in biphasic supersaturation assays.

Phase behavior of ASDs based on hydroxypropyl cellulose.

Novel polymeric carriers for amorphous solid dispersions (ASDs) are highly demanded in pharmaceutical industry to improve the bioavailability of poorly-soluble drug candidates. Besides established polymer candidates, hydroxypropyl celluloses (HPC) comes more and more into the focus of ASD production since they have the availability to stabilize drug molecules in aqueous media against crystallization. The thermodynamic long-term stability of HPC ASDs with itraconazole and fenofibrate was predicted in this work with PC-SAFT and compared to three-months enduring long-term stability studies.

Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation.

Background: An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis.

Methods: Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and an in-house RBD ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed.

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties.

In the past decade, prescriptions for opioid medicines have been exponentially increasing, instigating opioid abuse as a global health crisis associated with high morbidity and mortality. In particular, diversion from the intended mode of opioid administration, such as injecting and snorting the opioid, is a major problem that contributes to this epidemic. In light of this, novel formulation strategies are needed to support efforts in reducing the prevalence and risks of opioid abuse.

Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process.

Three-dimensional (3D) printing is revolutionising how we envision manufacturing in the pharmaceutical field. Here, we report for the first time the use of direct powder extrusion 3D printing: a novel single-step printing process for the production of printlets (3D printed tablets) directly from powdered materials. This new 3D printing technology was used to prepare amorphous solid dispersions of itraconazole using four different grades of hydroxypropylcellulose (HPC - UL, SSL, SL and L).