The Irritant Effects of Pharmaceutically Applied Surfactants

Dermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non-irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.     

A computer model of human atria with reasonable computation loadand realistic anatomical properties

Atrial fibrillation is the most frequent arrhythmia, provoking discomfort, heart failure and arterial embolisms. The aim of this work is to develop a simplified anatomical computer model of human atria for the study of atrial arrhythmias and the understanding of electrical propagation mechanisms. With the model we propose, up to 40 s of real-time propagation have been simulated on a single-processor computer. The size and the electrophysiological properties of the simulated atria are within realistic values and information about anatomy has been taken into account in a three-dimensional structure. Besides normal sinus beat, pathological phenomena such as flutter and fibrillation have been induced using a programmed stimulation protocol. One important observation in our model is that atrial arrhythmias are a combination of functional and anatomical reentries and that the geometry plays an important role. This virtual atrium can reproduce electrophysiological observations made in humans but with the advantage of showing in great detail how arrhythmias are initiated and sustained. Such details are difficult or impossible to study in humans. This model will serve us as a tool to evaluate the impact of new therapeutic strategies and to improve them.     

Preparation of a Solid Dispersion by a Dropping Methodto Improve the Rate of Dissolution of Meloxicam

Application of a solid dispersion system is one of the methods used to increase the bioavailability of poorly water-soluble drugs. Adaptation of the dropping method from the chemical industry as a formulation procedure may help the scaling-up process and simplify the formulation of poorly water-soluble compounds. Meloxicam (ME), a nonsteroidal anti-inflammatory drug that is poorly soluble in water, and polyethylene glycol (PEG) 4000, a water-soluble carrier, were formulated by using a dropping method in an attempt to improve the dissolution of ME. Pure ME and physical mixtures and tablets of ME–PEG 4000 (1:3 ratio) were compared as regards their dissolution with samples formulated by the dropping method. The results revealed that the round particles (solid drops) exhibited a higher dissolution rate than those of the physical mixtures, tablets, and pure ME. Self-modeling curve resolution (SMCR) as a chemometric method was used to evaluate X-ray powder diffractometry (XRPD) data. The results demonstrated the presence of a new crystalline phase in the solid dispersion, which can help the fast and quantitative dissolution from the solid drops. The round particles can be adapted to individual therapy by using a distributor.     

Formulation of tablets containing an 'in-process' amorphized active pharmaceutical ingredient

The aim of this work was a preliminary study of the "in-process" amorphization of clopidogrel hydrogensulfate (CLP) as model drug during the production of tablets as dosage form. A solvent method was used for amorphization and the crystalline phase of CLP was detected by differential scanning calorimetry; the physical parameters of fresh and stored tablets were investigated. For the amorphous form, Aerosil 200 was selected as crystallization inhibitor as the most suitable of eight auxiliary agents. The optimum composition of the product for amorphization in the scaling-up process (100-fold) was 7 parts of CLP to 3 parts of Aerosil 200. In this scaled-up product, the amorphous CLP was fixed on the surface of microcrystalline cellulose. The tablet form further stabilized the amorphous form. Finally, the steps of an "in-process" amorphization are given as a protocol, which can promote stabilization of an amorphized active pharmaceutical ingredient.     

Kinetics of the thermal decomposition of cellulose under the experimental conditions of thermal analysis. Theoretical extrapolations to high heating rates

Thermobalance-mass spectrometer (TG-MS) experiments carried out by the authors in a period of 8 years are reviewed and analyzed. Celluloses and lignocellulosic biomass samples were studied. The data are evaluated by the method of least squares. The results indicate that a single rate-controlling reaction step dominates the kinetics of the cellulose decomposition at low heating rates (2–20°C/min) provided that the heat and mass transport problems are experimentally eliminated and the amount of catalytic impurities is reduced by dilute acid or hot water washing treatments. The kinetic parameters obtained from the experiments with different cellulose and biomass samples evidenced only ca 8% scattering. A simple explanation is given for the kinetic compensation effect observed. Theoretical extrapolations are presented to predict the behavior of extremely small, idealized cellulose samples at high heating rates.     

Thermogravimetric/mass spectrometric characterization of the thermal decomposition of (4-O-methyl-D-glucurono)-D-xylan

A thermogravimetric/mass spectrometric (TG/MS) system was used to characterize the thermolysis reactions of (4-O-methyl-D -glucurono)-D -xylan. The mass spectrometric peaks, measured as function of time, were attributed to water, methanol, carbon monoxide, carbon dioxide, formaldehyde, formic acid, acetic acid, acetone, acrolein, 2-furaldehyde, and 3-hydroxy-2-penteno-1,5-lactone. The time derivative of the thermogravimetric curve (DTG) consisted of two partially overlapping peaks, indicating a multistep mechanism. The mass spectrometric intensities of the peaks assigned to methanol and 2-furaldehyde coincided with the first DTG peak, suggesting that the first DTG peak represents both dehydration and fragmentation pathways. Methanol, water, formyl group, and carbon dioxide contributed to both of the DTG peaks. This indicates that the dehydration, decarboxylation, and decarbonylation took place in two steps. The compounds observed only in the second DTG peak and later (acetone, formic acid, formaldehyde, acrolein, acetic acid, and 3-hydroxy-2-penteno-1,5-lactone) are probably products of reactions which occur after the collapse of the original polysaccharide structure.     

Preliminary analysis of COVID-19 academic information patterns: a call for open science in the times of closed borders

Scientometrics - The Pandemic of COVID-19, an infectious disease caused by SARS-CoV-2 motivated the scientific community to work together in order to gather, organize, process and distribute data...     

Preparation of a solid dispersion by a dropping method to improve the rate of dissolution of meloxicam

Application of a solid dispersion system is one of the methods used to increase the bioavailability of poorly water-soluble drugs. Adaptation of the dropping method from the chemical industry as a formulation procedure may help the scaling-up process and simplify the formulation of poorly water-soluble compounds. Meloxicam (ME), a nonsteroidal anti-inflammatory drug that is poorly soluble in water, and polyethylene glycol (PEG) 4000, a water-soluble carrier, were formulated by using a dropping method in an attempt to improve the dissolution of ME. Pure ME and physical mixtures and tablets of ME-PEG 4000 (1:3 ratio) were compared as regards their dissolution with samples formulated by the dropping method. The results revealed that the round particles (solid drops) exhibited a higher dissolution rate than those of the physical mixtures, tablets, and pure ME. Self-modeling curve resolution (SMCR) as a chemometric method was used to evaluate X-ray powder diffractometry (XRPD) data. The results demonstrated the presence of a new crystalline phase in the solid dispersion, which can help the fast and quantitative dissolution from the solid drops. The round particles can be adapted to individual therapy by using a distributor.     

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro–in silico lung deposition results

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways – carrier-based, carrier-free, and novel combined formulation – and thereby to compare their physicochemical and in vitro–in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs.

Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage.

Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage.

Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5?μm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.