Pharmaceutical Areas Research Articles

Antimicrobial Activity and Synergistic Antimicrobial Potential of Silver Nanoparticles against microbial contaminants isolated from pharmaceutical production areas

Antimicrobial Activity and Synergistic Antimicrobial Potential of Silver Nanoparticles against microbial contaminants isolated from pharmaceutical production areas

Sodium, potassium, calcium lactobionates, and lactobionic acid from Zymomonas mobilis: A novel approach about stability and stress tests

The bioproduction of lactobionic acid and its salts can be performed by enzymatic complex glucose-fructose oxidoreductase (GFOR) and glucono-δ-lactonase (GL) of Zymomonas mobilis. Considering the applicability of these compounds in pharmaceutical area, the aim of this study was to assess the accelerated and long-term stability studies of sodium, potassium, calcium lactobionate, and lactobionic acid. Furthermore, stress tests were performed to evaluate the stability against pH, temperature and oxidation. The samples submitted to degradation tests were analyzed by high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry analysis (HRMS-ESI-QTOF). Sodium, potassium, and calcium lactobionate were stable for six months of analyses considering the accelerated (40 °C and 75% RH) and long-term (30 °C and 75% RH) stability studies. The presence of lactobiono-δ-lactone and a significant increase in moisture were observed for both biosynthesized and commercially available lactobionic acid samples. Against the forced degradation tests, all the lactobionate salts and lactobionic acid showed to be stable upon alkaline and acid pH conditions, at 60 and 80 °C, and also against UV light exposition. Furthermore, the presence of lactobiono-δ-lactone form was observed in lactobionic acid samples. However, the degradation of both lactobionic acid and lactobionate salts was evident in the presence of hydrogen peroxide. This degradation kinetic profile suggests, that lactobionate salts follows a zero-order reaction model and lactobionic acid follows a second-order kinetic. The MS analysis of the main degradation product suggests a molecular formula C11H20O10 resulting from the oxidative decarboxylation. This report brings an amount of results as contribution to the scarce information regarding the chemical and physical-chemical stability of sodium, potassium, calcium lactobionate, and lactobionic acid. These data may be useful and serve as reference, in view of the multipurpose applications of the cited compounds.

In vitro cytotoxicity studies of industrial Eucalyptus kraft lignins on mouse hepatoma, melanoma and Chinese hamster ovary cells

Kraft lignin is a polyphenolic compound generated as a by-product from the kraft pulping process in large quantities annually worldwide. In addition to its commercial availability, its structural features make it worth to be considered in the pharmaceutical area. The present study was carried out to evaluate in vitro antioxidant and cytotoxic properties of kraft lignin on mouse hepatoma MH-22A, melanoma B16 (tumor cells) and Chinese hamster ovary (CHO, non-cancerous) cells. Moreover, several analytical techniques were used in order to elucidate the chemical structure of isolated industrial lignins (FT-IR, GPC, Py-GC–MS, 2D HSQC NMR). Results revealed high phenolic content in their composition, high-condensed structure and high phenolic hydroxyls group content. DPPH and ABTS⁎+ radical scavenging assays demonstrated their strong antioxidant activity, which was higher than found for commercial antioxidant (BHT). Kraft lignins act cytotoxically inducing apoptosis- and necrosis-like processes on both on tumor and normal cells. However, the results evidenced that MH-22A cells showed greater sensitive behavior than B16 and non-cancerous CHO cells, which were more tolerant of kraft lignin.

Modified release microcapsules loaded with red propolis extract obtained by spray-dryer technique

Biopolymers are currently one of the most interesting materials applied in the medical and pharmaceutical fields. The objective of this work was to develop the modified release microcapsules loaded with red propolis extract (RPE) using a spray-dryer technique. In addition, this manuscript characterizes this red propolis microcapsules using phytochemicals, thermal, physicochemical and dissolution test. The RPE was incorporated in the biopolymer solution, and then submitted to spray-dryer technique to obtain modified release microcapsules loaded with RPE; then, they were submitted to different physicochemical characterization technique through SEM analysis, FTIR, thermal analysis (TG and DSC), dissolution test and phytochemical assays. The red propolis microcapsules presented spherical morphology with particle size between 2.5 and 35 μm, when analyzed by SEM technique. The thermal analysis showed that the coating material decreases the thermo-oxidative degradation of the RPE in the microcapsules and according to the calorimetric curves (DSC) and infrared spectra the microencapsulation of the red propolis extract was obtained. The quantification of the bioactive compounds showed high amounts of total phenols (98.3%) and total flavonoids (92.9%) contents, and it was possible determinate the encapsulation degree in microcapsules. The red propolis microcapsules present high antioxidant capacity (90.6%) in sequestering the free radical DPPH˙. The dissolution tests demonstrate slow flavonoids release (between 70 and 100%) from the microcapsules and have proven to be modified release microcapsules during 12 h experiments. The red propolis microcapsules can be applied in pharmaceutical and nutraceutical areas due to modified release property, antioxidant and antibacterial activities.

Phenolic profile, antioxidant and antibacterial properties of Juglans regia L. (walnut) leaves from the Northeast of Portugal

Juglans regia L. (walnut tree) is a recognized source of bioactive compounds with potential health benefits. In this work, hydroethanolic extracts of J. regia leaves were obtained by heat assisted extraction from different Portuguese samples in two phenological stages (green and yellow leaves) aiming to assess the impact of seasonal variations. The samples were compared regarding their phenolic composition and bioactivity. Seventeen phenolic compounds were identified by liquid chromatography combined with a diode array detector and electrospray ionization mass spectrometer (LC-DAD-ESI/MSn): six phenolic acids, ten flavonoids and one tetralone derivative. The green leaves extracts presented a higher amount of total phenolic compounds (29.70 ± 0.03 mg/g extract) compared with the yellow leaves (23.26 ± 0.06 mg/g extract). In particular, yellow samples were richer in flavonoids (17.4 ± 0.2 mg/g extract; mainly quercetin-3-O-glucoside: 3.64 ± 0.01 mg/g extract), while the green ones presented higher phenolic acids content (16.7 ± 0.2 mg/g extract; mainly trans 3-p-coumaroylquinic acid: 6.9 ± 0.5 mg/g extract). Green leaves extract also presented higher antioxidant potential, achieving IC50 values around 32 ± 2 μg/mL and 26.8 ± 0.2 μg/mL for the oxidative haemolysis inhibition and the thiobarbituric acid reactive substances assays, respectively. Furthermore, only green leaves samples showed anti-inflammatory potential. The cytotoxic evaluations revealed similar anti-proliferative action of both extracts against the tumor cell lines tested. Also, an analogous anti-bacterial potential of the extracts was observed, with preferential action against Gram-positive clinical isolated bacteria, with lower minimum inhibitory concentration (MIC) values for Enterococcus faecalis and Listeria monocytogenes (MIC = 2.5 mg/mL). Therefore, the present study suggests the use of walnut leaves as a source of active ingredients without hepatotoxic effects to be used in different applications in the food or pharmaceutical areas.

A novel zinc-catalyzed Suzuki-type cross-coupling reaction of aryl boronic acids with alkynyl bromides

A novel Suzuki-type cross-coupling reaction of organoboron reagents with alkynyl bromides has been developed in the presence of catalytic Et2Zn/DMEDA system. The reaction afforded a variety of internal alkynes in moderate to excellent yields under mild reaction conditions without the formation of any homo-coupling products. The resulting internal alkynes have valuable applications in pharmaceutical and industrial areas. The use of relatively non-toxic zinc, chelating amine ligand and low reaction temperature make this protocol an alternative for the synthesis of internal alkynes. The scope and limitations of this protocol are also investigated.

Characterization, Purity Determination and Decomposition Kinetics of Ezetimibe Under Non-Isothermal Conditions

Background:Ezetimibe is a lipid-lowering agent used therapeutically alone or in combination of other drugs. The properties of the solid-state of drugs are critical factors in the pharmaceutical formulation development. Several instrumental techniques can be employed in the analysis of new formulations, but the thermoanalytical techniques, provide a fast and careful evaluation of physicochemical properties of a compound. </P><P> Objective: To carry out the physicochemical characterization, purity evaluation and non-isothermal kinetic studies of ezetimibe raw material.Methods:A combination of the following different analytical technics was employed: Differential Scanning Calorimetry, Thermogravimetric, Scanning Electron Microscopy, X-ray powder diffraction.Results:The results evidenced the crystalline characteristic of ezetimibe. The sample purity was 99.06 % ± 0.02 and the thermal decomposition followed a zero order kinetic, with activation energy of 96.56 kJ mol–1 and Arrhenius frequency factor of 3,442 x 109 min-1.Conclusion:The characterization of ezetimibe together with the non-isothermal kinetic degradation represents important studies for the pharmaceutical area, since it provides crucial information for the pharmacotechnical/quality control/production areas that should establish the specifications necessary to standardize the requirements of the raw material acquire to ensure the batch-to-batch reproducibility.

Concentration of exopolysaccharides produced by Fusarium fujikuroi and application of bioproduct as an effective bioherbicide

ABSTRACT Exopolysaccharides are secondary metabolites produced by microorganisms and are a subject of research in many fields of science and industry due to some of their confirmed properties, especially in the pharmaceutical and agrochemical areas. In this context, the objectives of this work were to evaluate the potential of Fusarium fujikuroi for producing exopolysaccharides and to concentrate such compounds in order to increase the herbicidal activity. Exopolysaccharides were produced by submerged fermentation and different concentration methods (membranes, lyophilization, and evaporation) were evaluated. The phytotoxic effects were assessed through absorption assays in detached leaves of Cucumis sativus and evaluated on the seventh day after application. The surface tension was evaluated for each concentration method. The production of exopolysaccharides in the crude broth without concentration was 5.94 g/L. When using the lyophilization method, a maximum yield of exopolysaccharides of 10.64 g/L was obtained. The membranes also presented satisfactory results of exopolysaccharides: 9.60 g/L. The increase of bioherbicidal activity and the lower surface tension are proportionally related to the increase of the concentration of exopolysaccharides.

Poly-ε-caprolactone (PCL), a promising polymer for pharmaceutical and biomedical applications: Focus on nanomedicine in cancer

Poly-ε-caprolactone (PCL) has been the subject of extensive research in the past few years. It is widely explored in drug delivery, where the development of nanomedicines for cancer, one of the major public health concerns nowadays, has not been the exception. As a biocompatible, biodegradable and bioresorbable polymer, PCL has also found plenty of uses in the form of microparticles and scaffolds; so is the main objective of the present review to emphasize its potential and present its properties along with applications in the pharmaceutical and biomedical area with a special focus on nanomedicine in cancer.

Terminalia belerica Mediated Green Synthesis of Nanoparticles of Copper, Iron and Zinc Metal Oxides as the Alternate Antibacterial Agents Against some Common Pathogens

The present work aims at the green synthesis of metal oxides of zinc, iron, and copper using the aqueous extract of Terminalia belerica as a reductant and stabilizer. The entire reaction process was simple, cost-effective, and convenient to handle without use of any other stabilizing or reducing agents. The successful formation of the metal oxide nanoparticles was confirmed by UV-vis spectroscopy. For thus-prepared nanoparticles were characterized, a series of techniques were employed including Fourier-transform infrared spectroscopy, X-ray diffraction spectroscopy, high-resolution transmission electron microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. We used these nanoparticles to demonstrate their antibacterial efficacy against some common standard bacterial pathogens including Staphylococcus aureus (ATCC-6538), Bacillus subtilis (MTCC-441), Escherichia coli (ATCC-8739), Klebsiella pneumoniae (ATCC-43816), and Salmonella enterica (MTCC-3858). The results indicate that these metal oxide nanoparticles may become a potential candidate for use in biological and pharmaceutical areas to fight against multi-drug resistant superbugs.

Characterization and study of the antibacterial mechanisms of silver nanoparticles prepared with microalgal exopolysaccharides

The green synthesis of biomaterials is of significant interest as it enables the safe and sustainable preparation of noble metallic nanoparticles for medical applications. Microalgae polysaccharides have received attention due to their outstanding properties such as biocompatibility, biodegradability and low cost. In addition, due to their variety of remarkable biological and physicochemical properties, polysaccharide-based nanoparticles have advantageous features yet to be explored. The primary objective of the current research was to investigate exopolysaccharides isolated from green microalgae Botryococcus braunii (EPBb) and Chlorella pyrenoidosa (EPCp), as both reducing and stabilizing agents, for the green synthesis of silver nanoparticles (AgNPs). Their antibacterial activity towards Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli), and antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus) was studied, as well as their cytotoxicity to human dermal fibroblasts. The presently synthesized AgNPs were spherical in shape and exhibited characteristic surface plasmon resonance at 430 nm. The main population had a particle size which ranged between 5 and 15 nm as analyzed by transmission electron micrographs. Zeta potentials averaged −51.81 ± 3.01 mV using EPBb and −12.16 ± 2.41 mV using EPCp. More importantly, AgNPs possessed strong antibacterial activity in a dose-dependent manner, even against drug-resistant bacteria. The enhanced antibacterial activity of these particles is explained due to extensive reactive oxygen species generation and bacterial cell membrane damage. In contrast, such AgNPs were not cytotoxic at the same therapeutic range to fibroblasts (0.5–10.0 μg/mL). In summary, these results showed that polysaccharide-capped AgNPs have a strong potential for numerous medical applications, such as antibacterial agents in pharmaceutical and biomedical areas.

THE INFLUENCE OF SALES FORCE AUTOMATION AND SALES TRAINING ON MEDICAL REPRESENTATIVE PERFORMANCE TO IMPROVE SALES EFFECTIVENESS

This research aims to analyze the influence of sales force automation and sales training on performance medical representative to increase the effectiveness of sales. The population of this research is a multinational pharmaceutical company employee work areas of Yogyakarta and Solo. Sample saturated samples were determined by the respondent, with the whole medical pharmaceutical multinational representative in Yogyakarta and Solo as much as 128 people. The data collection method is used with the kuisoner technique. Engineering analysis using model of causality. The results showed that the influence of the system: there is a sales force automation and sales training on performance medical representative; There is the influence of medical representative's performance against sales effectiveness; There is the influence of the system of sales force automation and sales training sales effectiveness against directly without going through the performance of medical representative in the multinational pharmaceutical companies.
 
 Keyword: Sales Force Automation, Sales Training, Performance, Effectiveness Of Sales

Structural and Rheological Properties of Pectins Extracted from Industrial Sugar Beet By-Products.

In this work, the efficient extraction of pectin from sugar beet by-products (pressed, ensiled and dried pulp), by using an acid method or a commercial cellulose, is accomplished. The extraction method had an impact on the pectin monomeric composition, mainly in xylose, arabinose, and galacturonic acid content, as determined by GC-FID. FTIR and SEC analyses allowed the determination of similar degrees of methoxylation and molecular weights, respectively, in the extracted pectins. The acid extraction of pectin in the ensiled by-product led to the highest yield (19%) with a galacturonic acid content of 46%, whereas the application of the enzymatic extraction method resulted in a lower yield (13%) but higher galacturonic acid content (72%). Moreover, the stability in aqueous solution as well as the emulsifying activity index was higher for pectin extracted by the acid method, whereas the viscosity was higher in pectin extracted by the enzymatic method. To the best of our knowledge, this is the first study analyzing the physicochemical properties and exploring the potential reuse of ensiled and dried by-products from sugar beet industry for the extraction of pectin to be further used in the food and pharmaceutical areas.

All Wrapped up: Stabilization of Enzymes within Single Enzyme Nanoparticles.

Enzymes are extremely useful in many industrial and pharmaceutical areas due to their ability to catalyze reactions with high selectivity. In order to extend their lifetime, significant efforts have been made to increase their stability using protein- or medium engineering as well as by chemical modification. Many researchers have explored the immobilization of enzymes onto carriers, or entrapment within a matrix, framework or nanoparticle with the hope of constricting the movement of the enzyme and shielding it from aggressive environments, thus delaying the denaturation. These strategies often balance three competing interests: (i) maintaining high enzymatic activity, (ii) ensuring good long-term stability against temperature, dehydration, organic solvents, and or aggressive pH, and (iii) enabling a tuning or reversible switching of enzyme activity. In most cases, multiple enzymes will be contained within a single nanoparticle or matrix, but in recent years researchers have begun to wrap up individual enzymes within single enzyme nanoparticles (SENs). In these nanoparticles the enzyme is stabilized by a thin shell, typically a polymer, prepared either by in situ polymerization from the enzyme surface or by assembling a preformed polymer around it. Because of the increased control over the environment directly around the enzyme, and the possibility of more directly controlling substrate diffusion, many SENs show remarkable stability while retaining high initial activities even for quite fragile enzymes. Moreover, the activity of the enzyme can often be more easily fine-tuned by adjusting the layer properties. We postulate that this emerging field will offer exciting and elegant opportunities to both extend the catalytic lifetime of enzymes in aggressive solvents, temperatures and pH, and enable their activity to be switched on and off on demand by modulation of the outer material layer.

A new, substituted palladacycle forppm level Pd-catalyzed Suzuki-Miyaura cross couplings in water.

A newly engineered palladacycle that contains substituents on the biphenyl rings along with the ligand HandaPhos is especially well-matched to an aqueous micellar medium, enabling valued Suzuki-Miyaura couplings to be run not only in water under mild conditions, but at 300 ppm of Pd catalyst. This general methodology has been applied to several targets in the pharmaceutical area. Multiple recyclings of the aqueous reaction mixture involving both the same as well as different coupling partners is demonstrated. Low temperature microscopy (cryo-TEM) indicates the nature and size of the particles acting as nanoreactors. Importantly, given the low loadings of Pd invested per reaction, ICP-MS analyses of residual palladium in the products shows levels to be expected that are well within FDA allowable limits.

Interpretation of the nexus between the entrepreneurs and entrepreneurial business opportunities in the healthcare context: a phenomenological study

Since few studies focused exclusively on the entrepreneurship, the entrepreneurial agents and their interaction with the business opportunities in the healthcare area, the purpose of this paper is to interpret the intersubjective nature of the interplay between the entrepreneurs and entrepreneurial business opportunities in the context of healthcare entrepreneurship. The paper's methodology is qualitative hermeneutic phenomenology. The samples of sixteen entrepreneurs in the pharmaceutical, medical biotechnology, medical devices and m-health areas of Iran were interviewed using semi-structured questions. Based on the interpretive phenomenological analysis approach, this study explores how healthcare entrepreneurs make sense of their business opportunities. The findings indicated seven spheres of the entrepreneurs' context-based insights, the entrepreneurs' context-based projections, the entrepreneurs' dispositional attributions, the external facilities in macro levels, the external facilities in micro levels, the entrepreneur's environmentally oriented actions and the entrepreneur's presupposition-oriented actions as the nature of the entrepreneurship nexus.

Blockchain in the social sphere of Smart Cities

The development of smart cities is based on the use of new technologies. One of these promising technologies is Blockchain. The use of Blockchain gives great opportunities for solving a complex of problems related to: ensuring energy efficiency in buildings, the introduction of sustainable energy technologies for megacities, the formation of eco-friendly settlements, etc. The article analyzes the possibilities of using Blockchain technology in the social sphere of the city. The analysis is carried out on the example of health and pharmaceuticals. The study was carried out in the framework of the institutional approach and the concept of economic opportunities. The objectives of the study were: to identify specific areas of use of Blockchain technology in the pharmaceutical and health care industries; to evaluate the role of this technology in ensuring compliance with medical standards, transparency and safety of drugs at all stages of their development, promotion and use; to determine the possibilities of technology in identifying more effective and high-quality treatment methods, their implementation in practical health care. The article presents the structure of the areas of pharmaceuticals and health care, where the Blockchain is used. The strategies are offered to reduce labour and energy costs for processing medical information, accelerating the creation of new treatment technologies and the creation of medicines, their implementation in practical health care..

Dimethylacrylamide gels linked by dimethacrylate cross-linkers

Poly(N,N-dimethylacrylamide) (PDMA) is a water-soluble and biocompatible polymer useful in biomedical, biotechnological and pharmaceutical application areas. In this study, dimethylacrylamide (DMA) units were connected with dimethacrylate chemical cross-linkers (DMA-xl) with various chain lengths to get homogeneous, biocompatible and mechanically strong DMA hydrogels and cryogels. In the first step, the effect of the distance between the vinyl groups of the cross-linker molecules on swelling and mechanical properties was investigated. While cross-linkers bearing longer ethylene glycol units from DMA-1 to DMA-2 bond more water molecules, DMA-9’s equilibrium swelling values are the lowest, which may be due to the better movement capability of the chains with longer cross-linker units that will increase the physical interactions between the molecules and lead to the more compact structures. In the second step, cross-linker ratio was changed with a fixed dimethacrylate group. When the mol ratio of DMA-2 is decreasing step by step from the highest to lowest concentration for the gels after synthesis, the elastic modulus decreases gradually from 30 to 6 kPa, and the gels show similar mechanical behavior in the swollen state. In the last step, the amount of cross-link units on the morphology of cryogels was investigated with DMA-2 gels. The results explicitly indicated that while the mesh size of PDMA cryogels decreased with an increase in DMA-2 concentration, the mechanical stability of the gels was increased.

Elucidating the interaction of Spathodea campanulata leaf extracts mediated potential bactericidal gold nanoparticles with human serum albumin: spectroscopic analysis

Nanomaterials in different form have been thoroughly used in the area of pharmaceutics and medicine for drug delivery. The large scale of nanoparticles (NPs) synthesis from plant extract is much safe, cheap and eco-friendly. Here, we demonstrated a new, one-step, ultra-fast biosynthesis of gold nanoparticles (sc-AuNPs, 19.54 nm) by using aqueous Spathodea campanulata leaf extracts as a reducing and capping agent. And also, we presented the synthesis of citrate capped gold nanoparticles (cit-AuNPs) of approximately same size (19.66 nm). These two NPs were characterized by UV-Visible, dynamic light scattering, transmission electron microscope and energy dispersive X-ray spectroscopy. Fourier transform infrared spectroscopy confirmed that the functional groups like OH, NH, OH of COOH and CO were contributed in the sc-AuNPs formation. The negative zeta potential (−20.5, −22.8 mV) established the stability and dispersion of the sc- and cit-AuNPs. The anti-bacterial activity of the sc- and cit-AuNPs were checked against Escherichia coli (DH5-Alpha). Minimum inhibitory concentration was 2.4 and 3.0 nM, respectively for sc- and cit-AuNPs. The interaction study of the sc-AuNPs/cit-AuNPs-human serum albumin (HSA) system was done by UV-Visible absorbance, fluorescence, circular dichroism, time resolved fluorescence spectroscopy and the measurement of zeta potential. Absorbance, three dimensional fluorescence, synchronous fluorescence and circular dichroism spectroscopy showed a minor conformational change of HSA upon interaction with the sc-AuNPs compared to cit-AuNPs. The present comparative study will advance our knowledge about the binding mode, mechanism and conformational change of the protein upon interaction with green synthesized sc-AuNPs and cit-AuNPs.Communicated by Ramaswamy H. Sarma

On-line rheological characterization of semi-solid formulations

The rheological profile of a semi-solid product is a critical quality attribute. To monitor changes of this attribute during manufacturing, it would be beneficial to measure the rheological parameters in an on-line or in-line mode and implement this as a part of a control strategy for manufacturing of semi-solids. None of the process analytical technology (PAT) tools for measuring the rheological parameters have yet been widely accepted in the pharmaceutical area, as most of the equipment can only measure viscosity. Therefore, an automated system based on the measurement of pressure difference across both a topology optimized channel and a tube geometry (capillary viscometer) was investigated. The Pressure Difference Apparatus (PDA) can sample from the bulk intermediate/product stream and press the sample through the apparatus at different flow rates to yield a frequency sweep (G′ and G″) and a flow curve (viscosity). A calibration model was successfully prepared and verified with hydroxyethyl cellulose gels with polymer content varying from 1.0 to 1.5% (w/w) resulting in gels of different viscosities. The calibration model was used on-line during manufacturing of a gel and manufacturing changes related to dilution of the product were clearly reflected in the batch evolution profiles. The measurements with the PDA reflected the shear rate and frequency ranges relevant for manufacturing and thereby complemented the rheology measurements obtained with a standard rheometer with real time data.