Search results for: pharmaceutical molecules

Authors: Muchun Yu, Xue Gao, Qian Chen

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As a novel passive vibration isolation technology, molecular spring isolator (MSI) is investigated in this paper. An MSI consists of water and hydrophobic zeolites as working medium. Under periodic excitation, water molecules intrude into hydrophobic pores of zeolites when the pressure rises and water molecules extrude from hydrophobic pores when pressure drops. At the same time, energy is stored, released and dissipated. An MSI of piston-cylinder structure was designed in this work. Experiments were conducted to investigate the stiffness properties of MSI. The results show that MSI exhibits high-static-low dynamic (HSLD) stiffness. Furthermore, factors such as the quantity of zeolites, temperature, and ions in water are proved to have an influence on the stiffness properties of MSI.

Keywords: hydrophobic zeolites, molecular spring, stiffness, vibration isolation

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Authors: Kanika Saxena, Sunita Balani

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Purpose - The aim of the study is to compare the reported sustainability activities in areas of emission, water management and gender equality, currently undertaken by the seven major pharmaceutical companies. Methodology: The published corporate sustainability activity reports for the year 2017 for seven pharmaceutical companies have been studied. The two main criteria for the inclusion of pharmaceutical companies in this study are that they are globally recognized and active in the field of sustainability reporting. Company’s actions and initiatives have been grouped under three categories: (i) Emissions (ii) Water management (iii) Gender Equality in terms of employee workforce. Findings: Based on the sustainability reports, quantification and grading of the companies showed interesting results. Johnson & Johnson and Bayer are leading their activities under emissions and water management categories. The number of activities under emission and water management in case of Eli Lily, Roche, Sanofi, Pfizer and GlaxoSmithKline were 19, 16, 16, 11 and 6 respectively. Johnson & Johnson and Eli Lily are leading in taking the initiatives to curb the problem of emissions as compared with other 5 companies. Under the category of gender equality in terms of employee workforce, Eli Lily is leading the group of sampled companies with 47% of women employee workforce globally followed by Sanofi with 46.2% (42.2% of managers) female employees. It has also been observed that in some of the reports, gender diversification in the workforce has not been mentioned though the total number of employees were mentioned. Conclusion: This study could serve as the informative material for future in-depth industry-specific studies in order to find out the participation of the pharmaceutical companies in the reporting of the sustainability activities especially in reference to emission, water management and gender equality in the workforce. In addition to it, this can be helpful as a reference point for other companies in the pharmaceutical sector who are yet to explore the field of sustainability initiatives and reporting. Due to the limited scope of this study, only seven major players of the pharmaceutical sector who are active in the field of sustainability have been considered.

Keywords: emission, gender equality workforce, pharmaceutical, sustainability, water management

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Authors: Sangil Han, In Su Kim

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Transition-metal-catalyzed C–H bond activation and its subsequent functionalization has been one of the most attractive topics in organic synthesis because of its remarkable potential for atom economy and environmental sustainability. In this addition, a variety of C(sp2)–H functionalization has been developed under metal catalysis in the past decade. Recently, much attention has been moved towards the C(sp3)–H functionalization events, which continue to be a challenging issue. In this area, directing group assisted sp3 C–H functionalization has been explored by use of amides, carboxylic acids, oximes, N-heterocycles, and etc. In particular, 8-methylquinolines have been found as good substrates for sp3 C–H functionalization due to its ability to form cyclometalated complexes. Succinimides have been recognized as privileged structural cores found in a number of bioactive natural products, pharmaceuticals, and functional materials. Furthermore, the reduced derivatives such as pyrrolidines and γ-lactams have been also found in a large number of pharmaceutical relevant molecules, thus making them one of the most important and promising compounds. We herein describe the first C(sp3)–H activation of 8-methylquinolines and subsequent functionalization with maleimides to afford various succinimide derivatives.

Keywords: C(sp3)–H activation, 8-methylquinolines, maleimides, succinimides

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Authors: Vidula Shevade, B. J. Nagare, Sajeev Chacko

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First principles simulation, meaning density functional theory (DFT) calculations with plane waves and pseudopotential, has become a prized technique in condensed matter theory. Nanoparticles (NP) have been known to possess good catalytic activities, especially for molecules such as CO, O₂, etc. Among the metal NPs, Aluminium based NPs are also widely known for their catalytic properties. Aluminium metal is a lightweight, excellent electrical, and thermal abundant chemical element in the earth’s crust. Aluminium NPs, when added to solid rocket fuel, help improve the combustion speed and considerably increase combustion heat and combustion stability. Adding aluminium NPs into normal Al/Al₂O₃ powder improves the sintering processes of the ceramics, with high heat transfer performance, increased density, and enhanced thermal conductivity of the sinter. We used VASP and Gaussian 0₃ package to compute the geometries, electronic structure, and bonding properties of Al₁₂Ni as well as its interaction with O₂ and CO molecules. Several MD simulations were carried out using VASP at various temperatures from which hundreds of structures were optimized, leading to 24 unique structures. These structures were then further optimized through a Gaussian package. The lowest energy structure of Al₁₂Ni has been reported to be a singlet. However, through our extensive search, we found a triplet state to be lower in energy. In our structure, the Ni atom is found to be on the surface, which gives the non-zero magnetic moment. Incidentally, O2 and CO molecules are also triplet in nature, due to which the Al₁₂-Ni cluster is likely to facilitate the oxidation process of the CO molecule. Our results show that the most favourable site for the CO molecule is the Ni atom and that for the O₂ molecule is the Al atom that is nearest to the Ni atom. Al₁₂Ni-O₂ and Al₁₂-Ni-CO structures we extracted using VMD. Al₁₂Ni nanocluster, due to in triplet electronic structure configuration, indicates it to be a potential candidate as a catalyst for oxidation of CO molecules.

Keywords: catalyst, gaussian, nanoparticles, oxidation

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Authors: Strahinja Z. Kovačević, Lidija R. Jevrić, Sanja O. Podunavac Kuzmanović

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The relationship between antibacterial activity of eighteen different substituted benzimidazole derivatives and their molecular characteristics was studied using chemometric QSAR (Quantitative Structure–Activity Relationships) approach. QSAR analysis has been carried out on inhibitory activity towards Staphylococcus aureus, by using molecular descriptors, as well as minimal inhibitory activity (MIC). Molecular descriptors were calculated from the optimized structures. Principal component analysis (PCA) followed by hierarchical cluster analysis (HCA) and multiple linear regression (MLR) was performed in order to select molecular descriptors that best describe the antibacterial behavior of the compounds investigated, and to determine the similarities between molecules. The HCA grouped the molecules in separated clusters which have the similar inhibitory activity. PCA showed very similar classification of molecules as the HCA, and displayed which descriptors contribute to that classification. MLR equations, that represent MIC as a function of the in silico molecular descriptors were established. The statistical significance of the estimated models was confirmed by standard statistical measures and cross-validation parameters (SD = 0.0816, F = 46.27, R = 0.9791, R2CV = 0.8266, R2adj = 0.9379, PRESS = 0.1116). These parameters indicate the possibility of application of the established chemometric models in prediction of the antibacterial behaviour of studied derivatives and structurally very similar compounds.

Keywords: antibacterial, benzimidazole, molecular descriptors, QSAR

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Authors: Lola Brasseur, Guillaume Caulier, Marie Demeyer, Pascal Gerbaux, Igor Eeckhaut

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Seawater being an ideal dispersing agent, chemical communication stays predominant in marine ecosystems. However, if many molecules acting in chemical heterospecific communication have already been well described in terrestrial ecosystems, only three of these molecules were identified in marine ecosystems. Echinoderms and their symbiotic organisms constitute very good models to study heterospecific chemical communication because each class synthesizes a specific type of molecules and symbioses with echinoderms as hosts are very usual. In this study, the chemical communication that allows the commensal shrimps Tuleariocaris holthuisi Hipeau-Jacquotte, 1965 to live with their host Echinometra mathaei (Blainville, 1825) was investigated. The chemoreception of the shrimp was characterized using olfactometers and it was demonstrated that hosts and synthetic hydroxynaphthoquinones are attractive to the symbiotic shrimps. Hydroxynaphthoquinonic pigments also known as spinochromes are by the way synthesized by sea urchin and involved in all probability in a lot of mechanisms. To our knowledge, this study is the first highlighting the ecological function of naphthoquinones as kairomones. Chemical extractions were also performed on sea urchins in order to analyze and identify their specific hydroxynaphthoquinones using HPLC-ESI-MS. Accurate mass identification and elemental composition have been performed on various organs (gonads, coelomic liquid, digestive system and test) in different morphotypes of Echinometra mathaei for a better understanding of the molecular diversity of these semiochemicals. Moreover, some experiments were performed to investigate the dependence of T. holthuisi for their host. First, the analyses showed that the molecules involved in shrimp pigmentation are the same that the ones involved in E. mathaei, suggesting a potential feeding on the host. Secondly, a substantial shrimp depigmentation and an increase of the mortality rate were demonstrated after the symbionts-host separation which could mean a potential implication of spinochromes in the shrimp metabolism.

Keywords: crustacean, sea urchin, spinochrome, symbiosis

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Authors: Amit Das

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Background and significance of the study: Generally investors and market forecasters use financial statement for investigation while it awakens contribute to investing. The main vicinity of financial accounting and reporting practices recommends a few basic financial performance indicators, namely, return on capital employed, return on assets and earnings per share, which is associated considerably with share prices. It is principally true in case of Indian pharmaceutical companies also. Share investing is intriguing a financial risk in addition to investors look for those financial evaluations which have noteworthy shock on share price. A crucial intention of financial statement analysis and reporting is to offer information which is helpful predominantly to exterior clients in creating credit as well as investment choices. Sound financial performance attracts the investors automatically and it will increase the share price of the respective companies. Keeping in view of this, this research work investigates the impact of financial performance indicators on share price of pharmaceutical companies in India which is listed in the Bombay Stock Exchange. Methodology: This research work is based on secondary data collected from moneycontrol database on September 28, 2015 of top 101 pharmaceutical companies in India. Since this study selects four financial performance indicators purposively and availability in the database, that is, earnings per share, return on capital employed, return on assets and net profits as independent variables and one dependent variable, share price of 101 pharmaceutical companies. While analysing the data, correlation statistics, multiple regression technique and appropriate test of significance have been used. Major findings: Correlation statistics show that four financial performance indicators of 101 pharmaceutical companies are associated positively and negatively with its share price and it is very much significant that more than 80 companies’ financial performances are related positively. Multiple correlation test results indicate that financial performance indicators are highly related with share prices of the selected pharmaceutical companies. Furthermore, multiple regression test results illustrate that when financial performances are good, share prices have been increased steadily in the Bombay stock exchange and all results are statistically significant. It is more important to note that sensitivity indices were changed slightly through financial performance indicators of selected pharmaceutical companies in India. Concluding statements: The share prices of pharmaceutical companies depend on the sound financial performances. It is very clear that share prices are changed with the movement of two important financial performance indicators, that is, earnings per share and return on assets. Since 101 pharmaceutical companies are listed in the Bombay stock exchange and Sensex are changed with this, it is obvious that Government of India has to take important decisions regarding production and exports of pharmaceutical products so that financial performance of all the pharmaceutical companies are improved and its share price are increased positively.

Keywords: financial performance indicators, share prices, pharmaceutical companies, India

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Authors: Manal Alhazmi, Artem Mishchenko

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A molecular fluids' behavior and interaction with other materials at the nanoscale is a complex process. Nanoscale fluids behave so differently than macroscale fluids and interact with other materials in unique ways. It is, therefore, feasible to understand the molecular behavior of H₂O in such two-dimensional nanoscale systems by studying (CaSO4-2H2O), commonly known as gypsum. In the present study, spectroscopic measurements on a 2D structure of exfoliated gypsum crystals are carried out by Raman and IR spectroscopy. An array of gypsum flakes with thicknesses ranging from 8nm to 100nm were observed and analyzed for their Raman and IR spectrum. Water molecules stretching modes spectra lines were also measured and observed in nanoscale gypsum flakes and compared with those of bulk crystals. CaSO4-2H2O crystals have Raman and infrared bands at 3341 cm-1 resulting from the weak hydrogen bonds between the water molecules. This internal vibration of water molecules, together with external vibrations with other atoms, are responsible for these bands. There is a shift of about 70 cm-1 In the peak position of thin flakes with respect to the bulk crystal, which is a result of the different atomic arrangement from bulk to thin flake on the nano scale. An additional peak was observed in Raman spectra around 2910-3137 cm⁻¹ in thin flakes but is missing in bulk crystal. This additional peak is attributed to a combined mode of water internal (stretching mode at 3394cm⁻¹) and external vibrations. In addition to Raman and infra- red analysis of gypsum 2D structure, electrical measurements were conducted to reveal the water molecules transport behavior in such systems. Electrical capacitance of the fabricated device is measured and found to be (0.0686 *10-12) F, and the calculated dielectric constant (ε) is (12.26).

Keywords: gypsum, infra-red spectroscopy, raman spectroscopy, H₂O behavior

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Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: Shilpi Tyagi, D. K. Nauriyal

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This study investigates the firm level determinants of profitability of Indian drug and pharmaceutical industry. The study uses inflation adjusted panel data for a period 2000-2013 and applies OLS regression model with Driscoll-Kraay standard errors. It has been found that export intensity, A&M intensity, firm’s market power and stronger patent regime dummy have exercised positive influence on profitability. The negative and statistically significant influence of R&D intensity and raw material import intensity points to the need for firms to adopt suitable investment strategies. The study suggests that firms are required to pay far more attention to optimize their operating expenditures, advertisement and marketing expenditures and improve their export orientation, as part of the long term strategy.

Keywords: Indian pharmaceutical industry, profits, TRIPS, performance

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Authors: Sakiru Badmos, David R. Cole, Alberto Striolo

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It is known that confinement in nm-size pores affects many structural and transport properties of water and co-existing volatile species. Of particular interest for fluids in sub-surface systems, in catalysis, and in separations are reports that confinement can enhance the solubility of gases in water. Equilibrium molecular dynamics simulations were performed for aqueous H₂S confined in slit-shaped silica pores at 313K. The effect of pore width on the H₂S solubility in water was investigated. Other properties of interest include the molecular distribution of the various fluid molecules within the pores, the hydration structure for solvated H₂S molecules, and the dynamical properties of the confined fluids. The simulation results demonstrate that confinement reduces the H₂S solubility in water and that the solubility increases with pore size. Analysis of spatial distribution functions suggests that these results are due to perturbations on the coordination of water molecules around H₂S due to confinement. Confinement is found to dampen the dynamical properties of aqueous H₂S as well. Comparing the results obtained for aqueous H₂S to those reported elsewhere for aqueous CH₄, it can be concluded that H₂S permeates hydrated slit-shaped silica nano-pores faster than CH₄. In addition to contributing to better understanding the behavior of fluids in subsurface formations, these observations could also have important implications for developing new natural gas sweetening technologies.

Keywords: confinement, interfacial properties, molecular dynamic simulation, sub-surface formations

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Authors: Betim Bahtiri, B. Arash, R. Rolfes

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Epoxy-based materials are frequently exposed to high-humidity environments in many engineering applications. As a result, their material properties would be degraded by water absorption. A full characterization of the material properties under hygrothermal conditions requires time- and cost-consuming experimental tests. To gain insights into the physics of diffusion mechanisms, atomistic simulations have been shown to be effective tools. Concerning the diffusion of water in polymers, spatial trajectories of water molecules are obtained from molecular dynamics (MD) simulations allowing the interpretation of diffusion pathways at the nanoscale in a polymer network. Conventional MD simulations of water diffusion in amorphous polymers lead to discrepancies at low temperatures due to the short timescales of the simulations. In the proposed model, this issue is solved by using a combined scheme of autonomous basin climbing (ABC) with kinetic Monte Carlo and reactive MD simulations to investigate the diffusivity of water molecules in epoxy resins across a wide range of temperatures. It is shown that the proposed simulation framework estimates kinetic properties of water diffusion in epoxy resins that are consistent with experimental observations and provide a predictive tool for investigating the diffusion of small molecules in other amorphous polymers.

Keywords: epoxy resins, water diffusion, autonomous basin climbing, kinetic Monte Carlo, reactive molecular dynamics

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Authors: Bongmun Kang, Kagnari Yamakawa, Yoshihisa Hagihara, Yuji Ito, Michimasa Kishimoto, Yoichi Kumada

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The PMMA-tag was genetically fused with the C-terminal region of VHH molecules. This antibody, VHH, is known as a single-chain domain, which is devoid of light chains. The PMMA-tag, which could affect the isoelectric point (pI) changeable with a charge of amino acid in VHHs were closely related to the solubility of VHH molecules during refolding. The genetic fusion of PMMA-tag to C-terminal region of VHHs significantly affects the recovery of their soluble protein during refolding by 50 mM TAPS at pH 8.5. It could be refolded with a recovery of more than 95% by dialysis at pH 8.5. A marked difference in the antigen-binding activities in the adsorption state was significantly high in VHH-PM compared to the wild type of VHH. There are approximately 8-fold differences in the antigen-binding activities in the adsorption state between VHH-PM and VHH.

Keywords: VHH, PMMA-tag, isoelectric point, pH, Solubility, refolding, immobilization, ELISA

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Authors: Muhammad Danyal Khan

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The standards of patentability are drawing a great impact upon medicine industry of Pakistan which is indirectly troubling the right to health of ordinary citizen. Globalization of intellectual property laws is directly impacting access to medicine for population in Pakistan. Pakistan has enacted Patent Ordinance 2000 to develop the standards of Patent laws in consonance with international commitments. Moreover, Pakistan is signatory to UN Millennium Development Goals (2000-2015), and three of them directly put stress upon the health standards. This article will provide a critical brief about implications of TRIPS Agreement on standards of health in Pakistan and will also propose a futuristic approach for the pharmaceutical industry. This paper will define the paradox of globalization and national preparedness on pharmaceutical patents utilizing industry statistics and case laws from Pakistan. Moreover, this work will contribute towards debate on access to medicine at legislative and interpretative levels that will further help development of equilibrium between pharmaceutical patents and right to health.

Keywords: TRIPS (Trade Related Intellectual Property Rights), patents, compulsory licensing, patent, lifesaving drugs, WTO, infringement

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Authors: Stephan Koehler, Thomas Friedli

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Performance measurement has evolved over time from a unidimensional short-term efficiency focused approach into a balanced multidimensional approach. Today, integrated performance measurement frameworks are often used to avoid local optimization and to encourage continuous improvement of an organization. In literature, the multidimensional characteristic of performance measurement is often described by competitive priorities. At the same time, on the highest abstraction level an effectiveness and efficiency dimension of performance measurement can be distinguished. This paper aims at a better understanding of the composition of effectiveness and efficiency and their relation in pharmaceutical quality control labs. The research comprises a lab-specific operationalization of effectiveness and efficiency and examines how the two dimensions are interlinked. The basis for the analysis represents a database of the University of St. Gallen including a divers set of 40 different pharmaceutical quality control labs. The research provides empirical evidence that labs with a high effectiveness also accompany a high efficiency. Lab effectiveness explains 29.5 % of the variance in lab efficiency. In addition, labs with an above median operational excellence performance have a statistically significantly higher lab effectiveness and lab efficiency compared to the below median performing labs.

Keywords: empirical study, operational excellence, performance measurement, pharmaceutical quality control lab

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Authors: Kumbharkhane Ashok

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The time domain dielectric relaxation spectroscopy (TDRS) probes the interaction of a macroscopic sample with a time-dependent electrical field. The resulting complex permittivity spectrum, characterizes amplitude (voltage) and time scale of the charge-density fluctuations within the sample. These fluctuations may arise from the reorientation of the permanent dipole moments of individual molecules or from the rotation of dipolar moieties in flexible molecules, like polymers. The time scale of these fluctuations depends on the sample and its relative relaxation mechanism. Relaxation times range from some picoseconds in low viscosity liquids to hours in glasses, Therefore the DRS technique covers an extensive dynamical process, its corresponding frequency range from 10-4 Hz to 1012 Hz. This inherent ability to monitor the cooperative motion of molecular ensemble distinguishes dielectric relaxation from methods like NMR or Raman spectroscopy which yield information on the motions of individual molecules. An experimental set up for Time Domain Reflectometry (TDR) technique from 10 MHz to 30 GHz has been developed for the aqueous solutions. This technique has been very simple and covers a wide band of frequencies in the single measurement. Dielectric Relaxation Spectroscopy is especially sensitive to intermolecular interactions. The complex permittivity spectra of aqueous solutions have been fitted using Cole-Davidson (CD) model to determine static dielectric constants and relaxation times for entire concentrations. The heterogeneous molecular interactions in aqueous solutions have been discussed through Kirkwood correlation factor and excess properties.

Keywords: liquid, aqueous solutions, time domain reflectometry

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Ilham Benali, Nasser Hajji, Nawfal Acha

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Given the fact that the pharmaceutical industry is a commonly studied sector in the context of innovation, the majority of innovation research is devoted to the developed markets known by high research and development (R&D) assets and intensive innovation. In contrast, in developing countries where R&D assets are very low, there is relatively little research to mention in the area of pharmaceutical sector innovation, characterized mainly by two principal elements which are the presence of foreign-owned firms and licensed manufacturing agreements between local firms and multinationals. With the scarcity of research in this field, this paper attempts to study the effect of these two elements on the firms’ innovation tendencies. Other traditional factors that influence innovation, which are the age and the size of the firm, the R&D activities and the market structure, revealed in the literature review, will be included in the study in order to try to make this work more exhaustive. The study starts by examining innovation tendency in pharmaceutical firms located in developing countries before analyzing the effect of foreign-owned firms and licensed manufacturing agreements between local firms and multinationals on technological, organizational and marketing innovation. Based on the related work and on the theoretical framework developed, there is a probability that foreign-owned firms and licensed manufacturing agreements between local firms and multinationals have a negative influence on technological innovation. The opposite effect is possible in the case of organizational and marketing innovation.

Keywords: developing countries, foreign owned firms, innovation, licensed manufacturing agreements, pharmaceutical industry

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Authors: T.C. Balachandra, Habibuddin Shaik

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This paper presents experimental results leading towards a better understanding of pre-breakdown and breakdown behavior of vacuum gaps under variable frequency alternating excitations. The frequency variation is in the range of 30 to 300 Hz in steps of 10 Hz for a fixed gap spacing of 0.5 mm. The results indicate that the pre-breakdown currents show an inverse relation with the breakdown voltage in general though erratic behavior was observed over a certain range of frequencies. A breakdown voltage peak was observed at 130 Hz. This was pronounced when the electrode pair was of stainless steel and less pronounced when copper and aluminum electrodes were used. The experimental results are explained based on F-N emission, I-F emission, and also thermal interaction due to quasi-continuous shower of anode micro-particles. Further, it is speculated that the ostensible cause for time delay between voltage and current peaks is due to the presence of neutral molecules in the gap.

Keywords: anode hot-spots, F-N emission, I-F emission, microparticle, neutral molecules, pre-breakdown conduction, vacuum breakdown

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Authors: Jing (Claire) LI

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The topic of corporate social responsibility (CSR) is significant for pharmaceutical companies in China at this current stage. This is because, as a rapid growth industry in China in recent years, the pharmaceutical industry in China has been undergone continuous and terrible incidents relating to CSR. However, there is limited research and practice of CSR in Chinese pharmaceutical companies. Also, there is an urgent call for more research in an international context to understand the implications of corporate life cycle on CSR performance. To respond to the research need and research call, this study examines the relationship between corporate life cycle and CSR performance of Chinese listed companies in pharmaceutical industry. This research studies Chinese listed companies in pharmaceutical industry for the period of 2010-2017, where the data is available in database. Following the literature, this study divides CSR performance with regards to CSR dimensions, including shareholders, creditors, employees, customers, suppliers, the government, and the society. This study uses CSR scores of HEXUN database and financial measures of these CSR dimensions to measure the CSR performance. This study performed regression analysis to examine the relationship between corporate life cycle stages and CSR performance with regards to CSR dimensions for pharmaceutical listed companies in China. Using cash flow pattern as proxy of corporate life cycle to classify corporate life cycle stages, this study found that most (least) pharmaceutical companies in China are in maturity (decline) stage. This study found that CSR performance for most dimensions are highest (lowest) in maturity (decline) stage as well. Among these CSR dimensions, performing responsibilities for shareholder is the most important among all CSR responsibilities for pharmaceutical companies. This study is the first to provide important empirical evidence from Chinese pharmaceutical industry on the association between life cycle and CSR performance, supporting that corporate life cycle is a key factor in CSR performance. The study expands corporate life cycle and CSR literatures and has both empirical and theoretical contributions to the literature. From perspective of empirical contributions, the findings contribute to the argument that whether there is a relationship between CSR performance and various corporate life cycle stages in the literature. This study also provides empirical evidence that companies in different corporate life cycles have difference in CSR performance. From perspective of theoretical contributions, this study relates CSR and stakeholders to corporate life cycle stages and complements the corporate life cycle and CSR literature. This study has important implications for managers and policy makers. First, the results will be helpful for managers to have an understanding in the essence of CSR, and their company’s current and future CSR focus over corporate life cycle. This study provides a reference for their actions and may help them make more wise resources allocation decisions of CSR investment. Second, policy makers (in the government, stock exchanges, and securities commission) may consider corporate life cycle as an important factor in formulating future regulations for companies. Future research can explore the "process-based" differences in CSR performance and more industries.

Keywords: China, corporate life cycle, corporate social responsibility, pharmaceutical industry

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Authors: Z. Derikvand, M. Dusek, V. Eigner

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One dimensional coordination polymer of Cdᴵᴵ based on pyrazine (pz) and 3-nitrophthalic acid (3-nphaH₂), namely poly[[diaqua bis(3-nitro-2-carboxylato-1-carboxylic acid)(µ₂-pyrazine) cadmium(II)]dihydrate], {[Cd(3-nphaH)2(pz)(H₂O)₂]. 2H₂O}ₙ was prepared and characterized. The asymmetric unit consists of one Cdᴵᴵ center, two (3-nphaH)– anions, two halves of two crystallographically distinct pz ligands, two coordinated and two uncoordinated water molecules. The Cdᴵᴵ cation is surrounded by four oxygen atoms from two (3-nphaH)– and two water molecules as well as two nitrogen atoms from two pz ligands in distorted octahedral geometry. Complicated hydrogen bonding network accompanied with N–O···π and C–O···π stacking interactions leads to formation of a 3D supramolecular network. Commonly, this kind of C–O–π and N–O···π interaction is detected in electron-rich CO/NO groups of (3-nphaH)– ligand and electron-deficient π-system of pyrazine.

Keywords: supramolecular chemistry, Cd coordination polymer, crystal structure, 3-nithrophethalic acid

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Authors: Farzad Khajavi

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Recognition of the interaction between active pharmaceutical ingredients (API) and excipients is a pivotal factor in the development of all pharmaceutical dosage forms. By predicting the interaction between API and excipients, we will be able to prevent the advent of impurities or at least lessen their amount. In this study, we used principle component analysis (PCA) to predict the interaction between Gliclazide as a secondary amine with Lactose in pharmaceutical solid dosage forms. The infrared spectra of binary mixtures of Gliclazide with Lactose at different mole ratios were recorded, and the obtained matrix was analyzed with PCA. By plotting score columns of the analyzed matrix, the incompatibility between Gliclazide and Lactose was observed. This incompatibility was seen experimentally. We observed the appearance of the impurity originated from the Maillard reaction between Gliclazide and Lactose at the chromatogram of the manufactured tablets in room temperature and under accelerated stability conditions. This impurity increases at the stability months. By changing Lactose to Mannitol and using Calcium Dibasic Phosphate in the tablet formulation, the amount of the impurity decreased and was in the acceptance range defined by British pharmacopeia for Gliclazide Tablets. This method is a fast and simple way to predict the existence of incompatibility between excipients and active pharmaceutical ingredients.

Keywords: PCA, gliclazide, impurity, infrared spectroscopy, interaction

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

Abstract:

Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

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Authors: J. Satya Eswari, Ch. Venkateswarlu

Abstract:

The formulation of a commercial pharmaceutical product involves several composition factors and response characteristics. When the formulation requires to satisfy multiple response characteristics which are conflicting, an optimal solution requires the need for an efficient multiobjective optimization technique. In this work, a regression is combined with a non-dominated sorting differential evolution (NSDE) involving Naïve & Slow and ε constraint techniques to derive different multiobjective optimization strategies, which are then evaluated by means of a trapidil pharmaceutical formulation. The analysis of the results show the effectiveness of the strategy that combines the regression model and NSDE with the integration of both Naïve & Slow and ε constraint techniques for Pareto optimization of trapidil formulation. With this strategy, the optimal formulation at pH=6.8 is obtained with the decision variables of micro crystalline cellulose, hydroxypropyl methylcellulose and compression pressure. The corresponding response characteristics of rate constant and release order are also noted down. The comparison of these results with the experimental data and with those of other multiple regression model based multiobjective evolutionary optimization strategies signify the better performance for optimal trapidil formulation.

Keywords: pharmaceutical formulation, multiple regression model, response surface method, radial basis function network, differential evolution, multiobjective optimization

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Authors: Blessing Atim Aderibigbe

Abstract:

A series of amine/ester-linked hybrid compounds containing pharmacophores, such as ursolic acid, oleanolic acid, ferrocene and bisphosphonates, were synthesized in an attempt to develop potent antibacterial and anticancer agents. Their structures were analyzed and confirmed using Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, and mass spectroscopy. All the synthesized hybrid compounds were evaluated for their antibacterial activities against eleven selected bacterial strains using a serial dilution method. Some of the compounds displayed significant antibacterial activity against most of the bacterial and fungal strains. In addition, the in vitro cytotoxicity of these compounds was also performed against selected cancer cell lines. Some of the compounds were also found to be more active than their parent compounds, revealing the efficacy of designing hybrid molecules using plant-based bioactive agents.

Keywords: ursolic acid, hybrid drugs, oleanolic acid, bisphosphonates

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Authors: Seokyoon Moon, Yun-Ho Ahn, Heejoong Kim, Sujin Hong, Yunseok Lee, Youngjune Park

Abstract:

Gas hydrate is a non-stoichiometric crystalline compound consisting of host water-framework and low molecular weight guest molecules. Small gaseous molecules such as CH₄, CO₂, and N₂ can be captured in the host water framework lattices of the gas hydrate with specific temperature and pressure conditions. The three well-known crystal structures of structure I (sI), structure II (sII), and structure H (sH) are determined by the size and shape of guest molecules. In this study, we measured the phase equilibria of binary (2,2-dimethyl-1-propanol + CO₂, CH₄, N₂) hydrates to explore their fundamental thermodynamic characteristics. We identified the structure of the binary gas hydrate by employing synchrotron high-resolution powder diffraction (HRPD), and the guest distributions in the lattice of gas hydrate were investigated via dispersive Raman and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopies. The end-to-end distance of 2,2-dimethyl-1-propanol was calculated to be 7.76 Å, which seems difficult to be enclathrated in large cages of sI or sII. However, due to the flexibility of the host water framework, binary hydrates of sI or sII types can be formed with the help of small gas molecule. Also, the synchrotron HRPD patterns revealed that the binary hydrate structure highly depends on the type of help gases; a cubic Fd3m sII hydrate was formed with CH₄ or N₂, and a cubic Pm3n sI hydrate was formed with CO₂. Interestingly, dispersive Raman and ¹³C NMR spectra showed that the unique tuning phenomenon occurred in binary (2,2-dimethyl-1-propanol + CO₂) hydrate. By optimizing the composition of NPA, we can achieve both thermodynamic stability and high CO₂ storage capacity for the practical application to CO₂ capture.

Keywords: clathrate, gas hydrate, neopentyl alcohol, CO₂, tuning phenomenon

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Authors: Gule Teri

Abstract:

The effective validation of analytical methods forms a crucial component of pharmaceutical manufacturing. However, traditional validation techniques can occasionally fail to fully account for inherent variations within datasets, which may result in inconsistent outcomes. This deficiency in validation accuracy is particularly noticeable when quantifying low concentrations of active pharmaceutical ingredients (APIs), excipients, or impurities, introducing a risk to the reliability of the results and, subsequently, the safety and effectiveness of the pharmaceutical products. In response to this challenge, we introduce an enhanced, tolerance-based Design of Experiments (DoE) approach for the validation of analytical methods. This approach distinctly measures variability with reference to tolerance or design margins, enhancing the precision and trustworthiness of the results. This method provides a systematic, statistically grounded validation technique that improves the truthfulness of results. It offers an essential tool for industry professionals aiming to guarantee the accuracy of their measurements, particularly for low-concentration components. By incorporating this innovative method, pharmaceutical manufacturers can substantially advance their validation processes, subsequently improving the overall quality and safety of their products. This paper delves deeper into the development, application, and advantages of this tolerance-based DoE approach and demonstrates its effectiveness using High-Performance Liquid Chromatography (HPLC) data for verification. This paper also discusses the potential implications and future applications of this method in enhancing pharmaceutical manufacturing practices and outcomes.

Keywords: tolerance-based design, design of experiments, analytical method validation, quality control, biopharmaceutical manufacturing

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Authors: Hideo Sawada

Abstract:

Fluoroalkyl end-capped oligomers [RF-(M)n-RF; RF = fluoroalkyl groups; M = radical polymerizable monomers] can form nanometre size-controlled self-assembled oligomeric aggregates through the aggregations of end-capped fluoroalkyl groups. Fluoroalkyl end-capped oligomeric aggregates can also interact with guest molecules to afford fluorinated aggregate/guest molecule nanocomposites; although the corresponding non-fluorinated oligomers cannot form such molecular aggregates to interact with guest molecules. For example, silica nanoparticles should act as guest molecules in fluorinated oligomeric aggregate cores to give new fluorinated oligomer-coated silica nanoparticles (fluorinated oligomer/silica nanocomposites). In these fluoroalkyl end-capped oligomers/silica nanocomposites, some fluorinated oligomers/silica nanocomposites were found to exhibit no weight loss behavior corresponding to the contents of oligomers in the silica matrices even after calcination at 800 oC. Fluoroalkyl end-capped vinyltrimethoxysilane oligomer-coated silica nanoparticles can be prepared by the sol-gel reaction of the corresponding fluorinated oligomer under alkaline conditions. The modified glass surface treated with this fluorinated oligomeric nanoparticle exhibited a completely super-hydrophobic characteristic. These fluorinated nanoparticles were also applied to the surface modification possessing a super-oleophobic characteristic. Not only fluoroalkyl end-capped oligomers but also low molecular weight fluorinated surfactants such as perfluoro-1,3-propanedisulfonic acid (PFPS) were applied to the preparation of fluorinated surfactants/silica nanocomposites to give no weight loss in proportion to the content of the surfactants in the nanocomposites even after calcination at 800 oC.

Keywords: fluorinated oligomer, silica nanocomposite, nonflammable characteristic, superamphiphobic chracteristic

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Authors: L. Spitaleri, C. M. A. Gangemi, R. Purrello, G. Nicotra, G. Trusso Sfrazzetto, G. Casella, M. Casarin, A. Gulino

Abstract:

Hybrid molecular–nanoparticle materials, obtained with a bottom-up approach, are suitable for the fabrication of functional nanostructures showing structural control and well-defined properties, i.e., optical, electronic or catalytic properties, in the perspective of applications in different fields of nanotechnology. Gold nanoparticles (Au NPs) exhibit important chemical, electronic and optical properties due to their size, shape and electronic structures. In fact, Au NPs containing no more than 30-40 atoms are only luminescent because they can be considered as large molecules with discrete energy levels, while nano-sized Au NPs only show the surface plasmon resonance. Hence, it appears that gold nanoparticles can alternatively be luminescent or plasmonic, and this represents a severe constraint for their use as an optical material. The aim of this work was the fabrication of nanoscale assembly of Au NPs covalently anchored to each other by means of novel bi-functional porphyrin molecules that work as bridges between different gold nanoparticles. This functional architecture shows a strong surface plasmon due to the Au nanoparticles and a strong luminescence signal coming from porphyrin molecules, thus, behaving like an artificial organized plasmonic and fluorescent network. The self-assembly geometry of this porphyrin on the Au NPs was studied by investigation of the conformational properties of the porphyrin derivative at the DFT level. The morphology, electronic structure and optical properties of the conjugated Au NPs – porphyrin system were investigated by TEM, XPS, UV–vis and Luminescence. The present nanostructures can be used for plasmon-enhanced fluorescence, photocatalysis, nonlinear optics, etc., under atmospheric conditions since our system is not reactive to air nor water and does not need to be stored in a vacuum or inert gas.

Keywords: gold nanoparticle, porphyrin, surface plasmon resonance, luminescence, nanostructures

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