Search results for: drug stability

Authors: Swarn Singh, Suruchi Singh

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In this paper, we present a fourth order two level implicit finite difference scheme for 1D Pennes bio-heat equation. Unconditional stability and convergence of the proposed scheme is discussed. Numerical results are obtained to demonstrate the efficiency of the scheme. In this paper we present a fourth order two level implicit finite difference scheme for 1D Pennes bio-heat equation. Unconditional stability and convergence of the proposed scheme is discussed. Numerical results are obtained to demonstrate the efficiency of the scheme.

Keywords: convergence, finite difference scheme, Pennes bio-heat equation, stability

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Authors: Iyd Eqqab Maree, Habil Jurgen Bast

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Vibration control of machines and structures incorporating viscoelastic materials in suitable arrangement is an important aspect of investigation. The use of viscoelastic layers constrained between elastic layers is known to be effective for damping of flexural vibrations of structures over a wide range of frequencies. The energy dissipated in these arrangements is due to shear deformation in the viscoelastic layers, which occurs due to flexural vibration of the structures. Multilayered cantilever sandwich beam like structures can be used in aircrafts and other applications such as robot arms for effective vibration control. These members may experience parametric instability when subjected to time dependant forces. The theory of dynamic stability of elastic systems deals with the study of vibrations induced by pulsating loads that are parametric with respect to certain forms of deformation. The purpose of the present work is to investigate the dynamic stability of a three layered symmetric sandwich beam (Drone Aircraft wings ) subjected to an end periodic axial force . Equations of motion are derived using finite element method (MATLAB software). It is observed that with increase in core thickness parameter fundamental buckling load increases. The fundamental resonant frequency and second mode frequency parameter also increase with increase in core thickness parameter. Fundamental loss factor and second mode loss factor also increase with increase in core thickness parameter. Increase in core thickness parameter enhances the stability of the beam. With increase in core loss factor also the stability of the beam enhances. There is a very good agreement of the experimental results with the theoretical findings.

Keywords: steel cantilever beam, viscoelastic material core, loss factor, transition region, MATLAB R2011a

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Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Flavia Laffleur, Andreas Bernkop-Schnürch

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Purpose: This study was aimed to investigate preactivated thiomers for their mucoadhesive potential. Methods: Accordingly, chitosan-thioglycolic-mercaptonicotinamide conjugates (chitosan-TGA-MNA) were synthesized by the oxidative S-S coupling of chitosan-thioglycolic acid (chitosan-TGA) with 6-mercaptonicotin amide (MNA). Unmodified chitosan, chitosan-TGA (thiomers) and chitosan-TGA-MNA conjugates were compressed into test discs to investigate cohesive properties, cytotoxicity assays and mucoadhesion studies. Results: Due to the immobilization of MNA, the chitosan-TGA-MNA conjugates exhibit comparatively higher swelling properties and cohesive properties corresponding unmodified chitosan. On the rotating cylinder, discs based on chitosan-TGA-MNA conjugates displayed 3.1-fold improved mucoadhesion time compared to thiolated polymers. Tensile study results were found in good agreement with rotating cylinder results. Moreover, preactivated thiomers showed higher stability. All polymers were found non-toxic over Caco-2 cells. Conclusion: On the basis of achieved results the pre activated thiomeric therapeutic agent seems to represent a promising generation of mucoadhesive polymers which are safe to use for a prolonged residence time to target the mucosa.

Keywords: biomedical application, drug delivery, polymer, thiomer

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Authors: Shabnam Dadparvar, Laijin Shen

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This paper focuses on China’s policy in the Middle East and the rivalry with the U.S. The question is that what are the main factors on China’s Middle East policy and its competition with the U.S? The hypothesis regards to three effective factors: 'China’s energy dependency' on the Middle East, 'economy' and support for 'stability' in the Middle East. What is important in China’s competition with the U.S regarding to its Middle East policy is the substantial difference in ways of treating the countries of the region; China is committed to Westphalia model based on non-interference in internal affairs of the countries and respect the sovereignty of the governments. However, after 9/11, the U.S is seeking a balance between stability and change through intervention in the international affairs and in some cases is looking for a regime change. From the other hand, China, due to its dependency on the region’s energy welcomes America’s military presence in the region for providing stability. The authors by using a descriptive analytical method try to explain the situation of rivalry between China and the United States in Middle East. China is an 'emerging power' with high economic growth and in demand of more energy supply. The problem is that a rising power in the region is often a source of concern for hegemony.

Keywords: China's foreign policy, energy, hegemony, the Middle East

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Authors: Nabil A. Albaser

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Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.

Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Tesfaye Alamirew Dessie

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Our study focuses on developing a Model Predictive Controller (MPC) and evaluating it against a traditional PID for a pasteurization process. Utilizing system identification from the experimental data, the dynamics of the pasteurization process were calculated. Using best fit with data validation, residual, and stability analysis, the quality of several model architectures was evaluated. The validation data fit the auto-regressive with exogenous input (ARX322) model of the pasteurization process by roughly 80.37 percent. The ARX322 model structure was used to create MPC and PID control techniques. After comparing controller performance based on settling time, overshoot percentage, and stability analysis, it was found that MPC controllers outperform PID for those parameters.

Keywords: MPC, PID, ARX, pasteurization

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Authors: Chang-Hwan Oh, Young-Jong Lee

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In April, 2015, the Ministry of Food and Drug Safety’s announcement that only 10 of the 207 products that list Cynanchum Wilfordii Radix among their ingredients were confirmed to actually contain “iyeobupiso” the counterfeit version of the “baeksuo” raised a fog to consumers who purchased health/functional foods supposedly containing the herbal medicinal material, “baeksuo” in Korean. Baeksuo is the main ingredient of the product “EstroG-100” that contain Phlomis umbrosa and Angelica gigas too (NaturalEndoTech, S.Korea). The hot water extract of the herbal medicinal materials (HMM) was approved as a product specific Health/Functional Food (HFF) having a helpful function to women reaching menopause by Korea Food & Drug Administration (Ministry of Food & Drug Safety at present). The origin of “baeksuo” is the root of Cynanchum wilfordii Hemsley in Korea (But “iyeobupiso, the root of Cynanchum auriculatum Royle ex Wight is considered as the origin of “baeksuo” in China). In Korea, about 116 HMMs are listed as the food materials in Korea Food Code among the total 187 HMMs could be used for food and medicine purpose simultaneously. But there are some chances of the HMMs (shared use for food and medicine purpose) could be misused by the part and HMMs not permitted for HFF such as the “baeksuo” case. In this study, some of HMMs (shared use for food and medicine purpose) are examined to alleviate the misuse chance of HMMs for HFFs in Korea. For the purpose of this study, the origin, shape, edible parts, efficacy and the side effects of the similar HMMs to be misused for HFF are investigated.

Keywords: herbal medicinal materials, healthy/functional foods, misuse, shared use

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Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

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Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

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Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

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Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

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Authors: A. Chellil, A. Nour, S. Lecheb, H.Mechakra, A. Bouderba, H. Kebir

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In this paper, the numerical study for the instability of a composite rotor is presented, under dynamic loading response in the harmonic analysis condition. The analysis of the stress which operates the rotor is done. Calculations of different energies and the virtual work of the aerodynamic loads from the rotor is developed. The use of the composite material for the rotor, offers a good Stability. Numerical calculations on the model develop of three dimensions prove that the damage effect has a negative effect on the stability of the rotor. The study of the composite rotor in transient system allowed to determine the vibratory responses due to various excitations.

Keywords: rotor, composite, damage, finite element, numerical

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Yuliani Aisyah, Sri Haryani, Novi Safriani

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Nutmeg oil is one of the essential oils that have the ability as an antibacterial so it potentially uses to inhibit the growth of undesirable microbes in food. However, the essential oil that has low solubility in water, high volatile content, and strong aroma properties is difficult to apply in to foodstuffs. Therefore, the oil-in-water nanoemulsion system was used in this research. Gelatin, lecithin and tween 80 with 10%, 20%, 30% concentrations have been examined for the preparation of nutmeg oil nanoemulsions. The physicochemical properties and stability of nutmeg oil nanoemulsion were analyzed on viscosity, creaming index, emulsifying activity, droplet size, and polydispersity index. The results showed that the type and concentration stabilizer had a significant effect on viscosity, creaming index, droplet size and polydispersity index (P ≤ 0,01). The nanoemulsions stabilized with tween 80 had the best stability because the creaming index value was 0%, the emulsifying activity value was 100%, the droplet size was small (79 nm) and the polydispersity index was low (0.10) compared to the nanoemulsions stabilized with gelatin and lecithin. In brief, Tween 80 is strongly recommended to be used for stabilizing nutmeg oil nanoemulsions.

Keywords: nanoemulsion, nutmeg oil, stabilizer, stability

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: Seyran Naghdi

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Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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Authors: Wasfi Al Salamat, Shaker Al-Kharouf

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This study aims to examine the determinants of financial stability for 13 commercial banks listed on the Amman stock exchange (ASE) over the period (2007-2016) after controlling for the independent variables: return on equity (ROE), return on assets (ROA), earnings per share (EPS), growth in gross domestic product (GDP), inflation rate and debt ratio to measure the financial stability by three main variables: capital adequacy, non-performing loans and the number of returned checks. The balanced panel data statistical approach has been used for data analysis. Results are estimated by using multiple regression models. The empirical results suggested that there is statistically significant negative effect of inflation rate and debt ratio on the capital adequacy while there is statistically significant positive effect of growth in gross domestic product on capital adequacy. In contrast, there is statistically significant negative effect of return on equity and growth in gross domestic product on the non-performing loans while there is statistically significant positive effect of inflation rate on non-performing loans. Finally, there is statistically significant negative effect of growth in gross domestic product on the number of returned checks while there is statistically significant positive effect of inflation rate on the number of returned checks.

Keywords: capital adequacy, financial stability, non-performing loans, number of returned checks, ASE

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Authors: Adil Loya, Kamran Maqsood, Muhammad Duraid

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Aerodynamic stability coefficients are necessary to be known before any unmanned aircraft flight is performed. This requires expertise on aerodynamics and stability control of the aircraft. To enable efficacious performance of aircraft requires that a well-defined flight path and aerodynamics should be defined beforehand. This paper presents a study on the aerodynamics of an unmanned aero vehicle (UAV) during flight conditions. Current research holds comparative studies of different parameters for flight aerodynamic, measured using two different open source analytical software programs. These software packages are DATCOM and XLRF5, which help in depicting the flight aerodynamic variables. Computational fluid dynamics (CFD) was also used to perform aerodynamic analysis for which Star CCM+ was used. Output trends of the study demonstrate high accuracies between the two software programs with that of CFD. It can be seen that the Coefficient of Lift (CL) obtained from DATCOM and XFLR is similar to CL of CFD simulation. In the similar manner, other potential aerodynamic stability parameters obtained from analytical software are in good agreement with CFD.

Keywords: XFLR5, DATCOM, computational fluid dynamic, unmanned aero vehicle

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Authors: Parisa Shirzadeh

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Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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Authors: Sarath Chandran Nair S, Srinivas Kodati, Vasudevan R, Asraff A. K

Abstract:

Spacecrafts generally employ liquid propulsion for their attitude and orbital maneuvers or raising it from geo-transfer orbit to geosynchronous orbit. Liquid propulsion systems use either mono-propellant or bi-propellants for generating thrust. These propellants are generally stored in either spherical tanks or cylindrical tanks with spherical end domes. The propellant tanks are provided with a propellant acquisition system/propellant management device along with vanes and their conical mounting structure to ensure propellant availability in the outlet for thrust generation even under a low/zero-gravity environment. Slosh is the free surface oscillations in partially filled containers under external disturbances. In a spacecraft, these can be due to control forces and due to varying acceleration. Knowledge of slosh and its effect due to internals is essential for understanding its stability through control stability studies. It is mathematically represented by a pendulum-mass model. It requires parameters such as slosh frequency, damping, sloshes mass and its location, etc. This paper enumerates various numerical and experimental methods used for evaluating the slosh parameters required for representing slosh. Numerical methods like finite element methods based on linear velocity potential theory and computational fluid dynamics based on Reynolds Averaged Navier Stokes equations are used for the detailed evaluation of slosh behavior in one of the spacecraft propellant tanks used in an Indian space mission. Experimental studies carried out on a scaled-down model are also discussed. Slosh parameters evaluated by different methods matched very well and finalized their dispersion bands based on experimental studies. It is observed that the presence of internals such as propellant management devices, including conical support structure, alters slosh parameters. These internals also offers one order higher damping compared to viscous/ smooth wall damping. It is an advantage factor for the stability of slosh. These slosh parameters are given for establishing slosh margins through control stability studies and finalize the spacecraft control system design.

Keywords: control stability, propellant tanks, slosh, spacecraft, slosh spacecraft

Procedia PDF Downloads 238

Authors: Hind Bouami, Patrick Millot

Abstract:

Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.

Keywords: Automated drug delivery systems, Hospitals, Human-centered automated system, Risk management

Procedia PDF Downloads 132

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 243

Authors: D. P. Evdokimov, A. N. Kirichenko, V. D. Blank, V. N. Denisov, B. A. Kulnitskiy

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In this study we investigated the stability of polyhedral carbon onions under influence of shear deformation and high pressures above 43 GPa by means of by transmission electron microscopy (TEM) and Raman spectroscopy (RS). It was found that at pressures up to 29 GPa and shear deformations of 40 degrees the onions are stable. At shear deformation applying at pressures above 30 GPa carbon onions collapsed with formation of amorphous carbon. At pressures above 43 GPa diamond-like carbon (DLC) was obtained.

Keywords: carbon onions, Raman spectroscopy, transmission electron spectroscopy

Procedia PDF Downloads 434

Authors: Rami Georg Johann

Abstract:

Against the background of the current geopolitical constellations, the author looks at various empire models, which are discussed and compared with each other with regard to their stability and functioning. The focus is on the fifth concept as a possible new world order in the 21st century. These will be discussed and compared to one another according to their stability and functioning. All empires to be designed will be conceptualised based on one, two, three, four, and five worlds. All worlds are made up of a different constellation of states and relating coalitions. All systems will be discussed in detail. The one-world-system, the“Western Empire,” will be presented as a possible solution to a new world order in the 21st century (fifth concept). The term “Western” in “Western Empire” describes the Western concept after World War II. This Western concept was the result of two horrible world wars in the 20th century.” With this in mind, the fifth concept forms a stable empire system, the “Western Empire,” by political measures tied to two issues. Thus, this world order provides a significantly higher long-term stability in contrast to all other empire models (comprising five, four, three, or two worlds). Confrontations and threats of war are reduced to a minimum. The two issues mentioned are “merger” and “competition.” These are the main differences in forming an empire compared to all empires and realms in the history of mankind. The fifth concept of this theory, the “Western Empire,” acts explicitly as a counter model. The Western Empire (fifth concept) is formed by the merger of world powers without war. Thus, a world order without competition is created. This merged entity secures long-term peace, stability, democratic values, freedom, human rights, equality, and justice in the new world order.

Keywords: empire formation, theory of international relations, Western Empire, world order

Procedia PDF Downloads 137

Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

Procedia PDF Downloads 371

Authors: Wadha Alqahtani

Abstract:

In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

Procedia PDF Downloads 110

Authors: D. Srinivasacharya, Nidhi Humnekar

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The goal of this research is to numerically investigate the convection of nanofluid flow in an inclined porous channel. Brownian motion and thermophoresis effects are accounted for by nanofluid. In addition, the flow in the porous region governs Brinkman’s equation. The perturbed state of the generalized eigenvalue problem is obtained using normal mode analysis, and Chebyshev spectral collocation was used to solve this problem. For various values of the governing parameters, the critical wavenumber and critical Rayleigh number are calculated, and preferred modes are identified.

Keywords: Brinkman model, inclined channel, nanofluid, linear stability, porous media

Procedia PDF Downloads 105

Authors: J. Cecrdle

Abstract:

This paper deals with the whirl flutter of the turboprop aircraft structures. It is focused on the influence of the blade lift span-wise distribution on the whirl flutter stability. Firstly it gives the overall theoretical background of the whirl flutter phenomenon. After that the propeller blade forces solution and the options of the blade lift modelling are described. The problem is demonstrated on the example of a twin turboprop aircraft structure. There are evaluated the influences with respect to the propeller aerodynamic derivatives and finally the influences to the whirl flutter speed and the whirl flutter margin respectively.

Keywords: aeroelasticity, flutter, propeller blade force, whirl flutter

Procedia PDF Downloads 528