Search results for: halal pharmaceutical

Authors: S. Mat Radzi, N. J. Abd Rahman, H. Mohd Noor, N. Ariffin

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Ferulic acid has widespread industrial potential by virtue of its antioxidant properties. However, it is partially soluble in aqueous media, limiting their usefulness in oil-based processes in food, cosmetic, pharmaceutical, and material industry. Therefore, modification of ferulic acid should be made by producing of more lipophilic derivatives. In this study, a preliminary investigation of lipase-catalyzed trans-esterification reaction of ethyl ferulate and olive oil was investigated. The reaction was catalyzed by immobilized lipase from Candida antarctica (Novozym 435), to produce ferulate ester, a sunscreen agent. A statistical approach of Response surface methodology (RSM) was used to evaluate the interactive effects of reaction temperature (40-80°C), reaction time (4-12 hours), and amount of enzyme (0.1-0.5 g). The optimum conditions derived via RSM were reaction temperature 60°C, reaction time 2.34 hours, and amount of enzyme 0.3 g. The actual experimental yield was 59.6% ferulate ester under optimum condition, which compared well to the maximum predicted value of 58.0%.

Keywords: ferulic acid, enzymatic synthesis, esters, RSM

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Authors: Lorena G. Calvo, Marta Lores, Trinidad de Miguel

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Natural extracts containing high polyphenolic concentration possess antibacterial and antifungal activity. The present research characterizes a hydro-organic extract with a high polyphenolic content as an antimicrobial candidate. As a result of this composition, the extract showed pronounced bioactivities with potential uses in agricultural, veterinary, pharmaceutical, and cosmetic industries. Polyphenol compounds were extracted by using hydro-organic solvent mixtures from the shrub Cytisus scoparius. The in vitro antimicrobial activity of this extract was evaluated on Gram-positive and Gram-negative bacteria and the fungus Candida albicans. Microbial species investigated, Bacillus cereus, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, are causing agents of several human and animal diseases. The extract showed activity against all tested species. So, it could be used for the development of biocides to control a wide range of pathogenic agents and contribute to the creation of economic and eco-friendly alternatives to antibiotics.

Keywords: antimicrobial properties, antioxidant properties, Cytisus scoparius, polyphenolic extract

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Authors: Dalia Almaghaslah

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Design thinking approach; empathize, define, ideate prototype, test, implement, was used to assess outpatient experiences in two hospital pharmacies in the Asir region, Saudi Arabia. Semi-structured interviews were conducted with 40 patients. The data were analyzed using thematic analysis. The findings suggested that patients were generally satisfied with pharmaceutical services provided in both pharmacies. Pharmacists were found to have enough knowledge, good attitude, and efficient communication and counselling skills. Non-pharmacy-related factors such as cultural factors (gender segregation), long waiting times, uncomfortable waiting areas, lack of electronic prescribing, number waiting system were found to have a negative impact on patients' experiences and satisfaction. Prototypes will be used to test the effects of implementing the electronic system in Al -mahal hospital and to test changing the physical layout of the waiting area in Asir hospital.

Keywords: design thinking, hospital pharmacy, patient satisfaction, Saudi Arabia

Procedia PDF Downloads 111

Authors: Guillaume Bélanger, Jean-Philippe Fontaine, Clémence Hauduc

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There is an undeniable thirst from organic chemists and from the pharmaceutical industry to access complex alkaloids with short syntheses. While medicinal chemists are interested in the fascinating wide range of biological properties of alkaloids, synthetic chemists are rather interested in finding new routes to access these challenging natural products of often low availability from nature. To synthesize complex polycyclic cores of natural products, reaction cascades or sequences performed one-pot offer a neat advantage over classical methods for their rapid increase in molecular complexity in a single operation. In counterpart, reaction cascades need to be run on substrates bearing all the required functional groups necessary for the key cyclizations. Chemoselectivity is thus a major issue associated with such a strategy, in addition to diastereocontrol and regiocontrol for the overall transformation. In the pursuit of synthetic efficiency, our research group developed an innovative one-pot transformation of linear substrates into bi- and tricyclic adducts applied to the construction of Aspidospermatan-type alkaloids. The latter is a rich class of indole alkaloids bearing a unique bridged azatricyclic core. Despite many efforts toward the synthesis of members of this family, efficient and versatile synthetic routes are still coveted. Indeed, very short, non-racemic approaches are rather scarce: for example, in the cases of aspidospermidine and aspidospermine, syntheses are all fifteen steps and over. We envisaged a unified approach to access several members of the Aspidospermatan alkaloids family. The key sequence features a highly chemoselective formamide activation that triggers a Vilsmeier-Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. Despite the high density and variety of functional groups on the substrates (electron-rich and electron-poor alkenes, nitrile, amide, ester, enol ether), the sequence generated three new carbon-carbon bonds and three rings in a single operation with good yield and high chemoselectivity. A detailed study of amide, nucleophile, and dipolarophile variations to finally get to the successful combination required for the key transformation will be presented. To complete the indoline fragment of the natural products, we developed an original approach. Indeed, all reported routes to Aspidospermatan alkaloids introduce the indoline or indole early in the synthesis. In our work, the indoline needs to be installed on the azatricyclic core after the key cyclization sequence. As a result, typical Fischer indolization is not suited since this reaction is known to fail on such substrates. We thus envisaged a unique photocatalyzed decarboxylative radical cyclization. The development of this reaction as well as the scope and limitations of the methodology, will also be presented. The original Vilsmeier-Haack and azomethine ylide cyclization sequence as well as the new photocatalyzed decarboxylative radical cyclization will undoubtedly open access to new routes toward polycyclic indole alkaloids and derivatives of pharmaceutical interest in general.

Keywords: Aspidospermatan alkaloids, azomethine ylide cycloaddition, decarboxylative radical cyclization, indole and indoline synthesis, one-pot sequential cyclizations, photocatalysis, Vilsmeier-Haack Cyclization

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Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: Ana L. Sánchez Regla, Igor A. Rivera González, María del Pilar Monserrat Pérez Hernández

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The ability of an organization to identify and get useful information from external sources, assimilate it, transform and apply to generate products or services with added value is called absorptive capacity. Absorptive capabilities contribute to have market opportunities to firms and get a leader position with respect to others competitors. The Bioprocess Development and Research Unit (UDIBI) is a Research and Development (R&D) laboratory that belongs to the National Polytechnic Institute (IPN), which is a higher education institute in Mexico. The UDIBI was created with the purpose of carrying out R and D activities for the Transferon®, a biopharmaceutical product developed and patented by IPN. The evolution of competence and scientific and technological platform made UDIBI expand its scope by providing technological services (preclínical studies and bio-compatibility evaluation) to the national pharmaceutical industry and biopharmaceutical industry. The relevance of this study is that those industries are classified as high scientific and technological intensity, and yet, after a review of the state of the art, there is only one study of absorption capabilities in biopharmaceutical industry with a similar scope to this research; in the case of Mexico, there is none. In addition to this, UDIBI belongs to a public university and its operation does not depend on the federal budget, but on the income generated by its external technological services. This fact represents a highly remarkable case in Mexico's public higher education context. This current doctoral research (2015-2019) is contextualized within a case study, its main objective is to identify and analyze the absorptive capabilities that characterise the UDIBI that allows it had become in a one of two third authorized laboratory by the sanitary authority in Mexico for developed bio-comparability studies to bio-pharmaceutical products. The development of this work in the field is divided into two phases. In a first phase, 15 interviews were conducted with the UDIBI personnel, covering management levels, heads of services, project leaders and laboratory personnel. These interviews were structured under a questionnaire, which was designed to integrate open questions and to a lesser extent, others, whose answers would be answered on a Likert-type rating scale. From the information obtained in this phase, a scientific article was made (in review and a proposal of presentation was submitted in different academic forums. A second stage will be made from the conduct of an ethnographic study within this organization under study that will last about 3 months. On the other hand, it is intended to carry out interviews with external actors around the UDIBI (suppliers, advisors, IPN officials, including contact with an academic specialized in absorption capacities to express their comments on this thesis. The inicial findings had shown two lines: i) exist institutional, technological and organizational management elements that encourage and/or limit the creation of absorption capacities in this scientific and technological laboratory and, ii) UDIBI has had created a set of multiple transfer technology of knowledge mechanisms which have had permitted to build a huge base of prior knowledge.

Keywords: absorptive capabilities, biopharmaceutical industry, high research and development intensity industries, knowledge management, transfer of knowledge

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Authors: Andualem Workie

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In this study, we examined the sinterability and bioactivity of MgO-SiO₂-P₂O₅-CaO-CaF₂ glass compositions created through spray pyrolysis. We evaluated the bioactivity of the materials by immersing them for varying periods of time in simulated bodily fluid (SBF) and found that bioactivity was related to the sintering temperature and soaking time. The material's pH value during immersion in SBF was within the range of 7.4-8.2, which is below 8.5 and improves compatibility and reduces toxicity in biological applications. We used X-ray diffraction and scanning electron microscopy to determine the phase compositions and morphologies of the samples and found that the 1100°C sintered A-W GC sample exhibited the highest bioactivity after soaking in SBF. This sample was dominated by fluorapatite, wollastonite, and whitlockite crystals scattered throughout the glass matrix. The crystallinity (%) of the A-W GC increased as its bioactivity improved, making it more suitable for use in pharmaceutical applications. We also conducted a cytotoxicity test on A-W GC samples sintered at different temperatures and found that the glass-ceramics were non-toxic to MC3T3-E1 cells at all extraction concentrations, except for those sintered at 700°C at concentrations of 250, 200, and 150 mg/ml where cell viability (%) was below the threshold of 70%.

Keywords: apatite wollastonite glass ceramics, bioactivity, calcination, cell viability

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Authors: Amelia Tero-Vescan, Camil-Eugen Vari, Laura Ciulea, Cristina Filip, Silvia Imre

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A HPLC –UV method for the identification of ephedrine (EPH), sibutramine (SB), yohimbine (Y) and caffeine (CF) was developed. Separation was performed on a Kromasil 100-RP8, 150 mm x 4.6 mm, 5 mm column equipped with a precolumn Kromasil RP 8. Mobile phase was a gradient of 80-35 % sodium dihydrogen phosphate pH=5 with NH4OH and acetonitrile over 15 minutes time of analysis. Based on the responses of 113 athletes about dietary supplements (DS) consumed for "fat burning" and weight loss which have a legal status in Romania, 28 supplements have been selected and investigated for their content in CF, Y, legal substances, and SB, EPH (prohibited substances in DS). The method allows quantitative determination of the four substances in a short analysis time and with minimum cost. The presence of SB and EPH in the analyzed DS was not detected while the content in CF and Y considering the dosage recommended by the manufacturer does not affect the health of the consumers. DS labeling (plant extracts with CF and Y content) allows manufacturers to avoid declaring correct and exact amounts per pharmaceutical form (pure CF or equivalent and Y, respectively).

Keywords: dietary supplements, sibutramine, ephedrine, yohimbine, caffeine, HPLC

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Authors: Amira M. Hassanein, Nehal A. Salahuddin, Atsunori Matsuda, Toshiaki Hattori, Mona N. Elfiky

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New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work. This was achieved by exploring the interesting properties of conductive (Mg/Al) layered double hydroxide- Dodecyl Sulphate/Polypyrrole nanocomposites which were synthesized by in-situ polymerization of pyrrole during the assembly of (Mg/Al) layered double hydroxide, and by employing the anionic surfactant Dodecyl sulphate as a modifier. The morphology and surface area of the nanocomposites changed with the percentage of Pyrrole. Under optimal conditions, the modified carbon paste electrode successfully achieved detection limits of 0.057 and 0.134 nmol.L-1 of Terazosin hydrochloride in pharmaceutical formulation and spiked human serum fluid, respectively. Moreover, the sensors are highly stable, reusable, and free from interference by other commonly present excipients in drug formulations.

Keywords: layered double hydroxide, polypyrrole, terazosin hydrochloride, square-wave adsorptive anodic stripping voltammetry

Procedia PDF Downloads 191

Authors: Miguel A. Figueroa, José A. Lara-Ramos, Miguel A. Mueses

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Pharmaceutical residues are a section of emerging contaminants of anthropogenic origin that are present in a myriad of waters with which human beings interact daily and are starting to affect the ecosystem directly. Conventional waste-water treatment systems are not capable of degrading these pharmaceutical effluents because their designs cannot handle the intermediate products and biological effects occurring during its treatment. That is why it is necessary to hybridize conventional waste-water systems with non-conventional processes. In the specific case of an ozonation process, its efficiency highly depends on a perfect dispersion of ozone, long times of interaction of the gas-liquid phases and the size of the ozone bubbles formed through-out the reaction system. In order to increase the efficiency of these parameters, the use of a modified flotation cell has been proposed recently as a reactive system, which is used at an industrial level to facilitate the suspension of particles and spreading gas bubbles through the reactor volume at a high rate. The objective of the present work is the development of a mathematical model that can closely predict the kinetic rates of reactions taking place in the flotation cell at an experimental scale by means of identifying proper reaction mechanisms that take into account the modified chemical and hydrodynamic factors in the FeO-catalyzed Ozonation of Diclofenac aqueous solutions in a flotation cell. The methodology is comprised of three steps: an experimental phase where a modified flotation cell reactor is used to analyze the effects of ozone concentration and loading catalyst over the degradation of Diclofenac aqueous solutions. The performance is evaluated through an index of utilized ozone, which relates the amount of ozone supplied to the system per milligram of degraded pollutant. Next, a theoretical phase where the reaction mechanisms taking place during the experiments must be identified and proposed that details the multiple direct and indirect reactions the system goes through. Finally, a kinetic model is obtained that can mathematically represent the reaction mechanisms with adjustable parameters that can be fitted to the experimental results and give the model a proper physical meaning. The expected results are a robust reaction rate law that can simulate the improved results of Diclofenac mineralization on water using the modified flotation cell reactor. By means of this methodology, the following results were obtained: A robust reaction pathways mechanism showcasing the intermediates, free-radicals and products of the reaction, Optimal values of reaction rate constants that simulated Hatta numbers lower than 3 for the system modeled, degradation percentages of 100%, TOC (Total organic carbon) removal percentage of 69.9 only requiring an optimal value of FeO catalyst of 0.3 g/L. These results showed that a flotation cell could be used as a reactor in ozonation, catalytic ozonation and photocatalytic ozonation processes, since it produces high reaction rate constants and reduces mass transfer limitations (Ha > 3) by producing microbubbles and maintaining a good catalyst distribution.

Keywords: advanced oxidation technologies, iron oxide, emergent contaminants, AOTS intensification

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Authors: Deokyeong Choe, Sung Hun Youn, Younggon Kim, Chul Soo Shin

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L-Cysteine, a sulfur-containing amino acid, has been often used in the pharmaceutical, cosmetic, food, and feed additive industries. This amino acid has been usually produced by acid-hydrolysis of human hair and poultry feathers. There are many problems, such as avoidance for use of animal hair, low yields, and formation of harmful waste material. As an alternative, the enzymatic conversion of D, L-2-amino-Δ2-thiazoline-4-carboxylic acid (ATC) to L-cysteine has been developed as an environmental-friendly method. However, the substrate solubility was too low to be used in industry. In this study, high concentrations of eutectic substrate solutions were prepared to solve the problem. Eutectic melting occurred at 39°C after mixing ATC and malonic acid at a molar ratio of 1:1. The characteristics of eutectic mixtures were analyzed by FE-SEM, EDS mapping, and XPS. However, since sorbitol, MnSO4, and NaOH should be added as supplements to the substrate mixture for the activation and stabilization of the enzyme, strategies for sequential addition of total five compounds, ATC, malonic acid, sorbitol, MnSO4, and NaOH were established. As a result, eutectic substrate mixtures of 670 mM ATC were successfully formulated. After 6 h of enzymatic reaction, 550 mM L-cysteine was made.

Keywords: D, L-2-amino-Δ2-thiazoline-4-carboxylicacid, enzymatic conversion, eutectic solution, l-cysteine

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Authors: Antonella Di Sotto, Cinzia Ingallina, Caterina Fraschetti, Simone Circi, Marcello Locatelli, Simone Carradori, Gabriela Mazzanti, Luisa Mannina, Silvia Di Giacomo

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Cannabis sativa L. is one of the oldest cultivated plant species known not only for its voluptuous use but also for the wide application in food, textile, and therapeutic industries. Recently, the progress of biotechnologies applied to medicinal plants has allowed to produce different hemp varieties with low content of psychotropic phytoconstituents (tetrahydrocannabinol < 0.2% w/v), thus leading to a renewed industrial and therapeutic interest for this plant. In this context, in order to discover new potential remedies of pharmaceutical and/or nutraceutical interest, the chemopreventive properties of different organic and hydroalcoholic extracts, obtained from the inflorescences of C. sativa L. var. USO31, collected in June and September harvesting, were assessed. Particularly, the antimutagenic activity towards the oxidative DNA-damage induced by tert-butyl hydroperoxide (t-BOOH) was evaluated, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging power of the samples were assessed as possible mechanisms of antimutagenicity. Furthermore, the ability of the extracts to inhibit the glucose-6-phosphate dehydrogenase (G6PD), whose overexpression has been found to play a critical role in neoplastic transformation and tumor progression, has been studied as a possible chemopreventive strategy. A careful phytochemical characterization of the extracts for phenolic and terpenoid composition has been obtained by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Under our experimental condition, all the extracts were found able to interfere with the tBOOH-induced mutagenicity in WP2uvrAR strain, although with different potency and effectiveness. The organic extracts from both the harvesting periods were found to be the main effective antimutagenic samples, reaching about a 55% inhibition of the tBOOH-mutagenicity at the highest concentration tested (250 μg/ml). All the extracts exhibited radical scavenger activity against DPPH and ABTS radicals, with a higher potency of the hydroalcoholic samples. The organic extracts were also able to inhibit the G6PD enzyme, being the samples from September harvesting the highly potent (about 50% inhibition respect to the vehicle). At the phytochemical analysis, all the extracts resulted to contain both polar and apolar phenolic compounds. The HPLC analysis revealed the presence of catechin and rutin as the major constituents of the hydroalcoholic extracts, with lower levels of quercetin and ferulic acid. The monoterpene carvacrol was found to be an ubiquitarian constituent. At GC-MS analysis, different terpenoids, among which caryophyllene sesquiterpenes, were identified. This evidence suggests a possible role of both polyphenols and terpenoids in the chemopreventive properties of the extracts from the inflorescences of C. sativa var. USO31. According to the literature, carvacrol and caryophyllene sesquiterpenes can contribute to the strong antimutagenicity although the role of all the hemp phytocomplex cannot be excluded. In conclusion, present results highlight a possible interest for the inflorescences of C. sativa var. USO31 as source of bioactive molecules and stimulate further studies in order to characterize its possible application for nutraceutical and pharmaceutical purposes.

Keywords: antimutagenicity, glucose-6-phosphate dehydrogenase, hemp inflorescences, nutraceuticals, sesquiterpenes

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Authors: Norhidayah Suleiman, Afza Zulfaka

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Zingiber officinale var. Bentong has been identified as the source of high added value compound specifically gingerol-related compounds. The extraction of the high-value compound using conventional method resulted in low yield and time consumption. Hence, the motivation for this work is to investigate the effect of the extraction technique on the essential oil from Zingiber officinale var. Bentong rhizome for commercialization purpose in many industries namely, functional food, pharmaceutical, and cosmeceutical. The investigation begins with a pre-treatment using ultrasound assisted in order to enhance the recovery of essential oil. It was conducted at a fixed frequency (20 kHz) of ultrasound with various time (10, 20, 40 min). The extraction using supercritical carbon dioxide (scCO2) were carried out afterward at a specific condition of temperature (50 °C) and pressure (30 MPa). scCO2 extraction seems to be a promising sustainable green method for the extraction of essential oil due to the benefits that CO2 possesses. The expected results demonstrated the ultrasound-assisted-scCO2 produces a higher yield of essential oil compared to solely scCO2 extraction. This research will provide important features for its application in food supplements or phytochemical preparations.

Keywords: essential oil, scCO2, ultrasound assisted, Zingiber officinale Var. Bentong

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Authors: Shahnaz Mansouri, David Martin, Xiao Dong Chen, Meng Wai Woo

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Ultrafine hydrophobic and non-water-soluble drugs can increase the percentage of absorbed compared to their initial dosage. This paper provides a scalable new method of making ultrafine particles of substantially insoluble water compounds specifically, submicron particles of ethanol soluble and water insoluble pharmaceutical materials by steaming an ethanol droplet to prepare a suspension and then followed by immediate drying. This suspension is formed by adding evaporated water molecules as an anti-solvent to the solute of the samples and in early stage of precipitation continued to dry by evaporating both solvent and anti-solvent. This fine particle formation has produced fast dispersion powder in water. The new method is an extension of the antisolvent vapour precipitation technique which exposes a droplet to an antisolvent vapour with reference to the dissolved materials within the droplet. Ultrafine vitamin D3 and ibuprofen particles in the submicron ranges were produced. This work will form the basis for using spray dryers as high-throughput scalable micro-precipitators.

Keywords: single droplet drying, nano size particles, non-water-soluble drugs, precipitators

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Authors: A. Benmoussa, M. Bouanini, M. Rebhi

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The mixing and agitation of fluid in stirred tank is one of the most important unit operations for many industries such as chemical, biotechnological, pharmaceutical, petrochemical, cosmetic, and food processing. Therefore, determining the level of mixing and overall behaviour and performance of the mixing tanks are crucial from the product quality and process economics point of views. The most fundamental needs for the analysis of these processes from both a theoretical and industrial perspective is the knowledge of the hydrodynamic behaviour and the flow structure in such tanks. Depending on the purpose of the operation carried out in mixer, the best choice for geometry of the tank and agitator type can vary widely. Initially, a local and global study namely the velocity and power number on a typical agitation system agitated by a mobile-type two-blade straight (d/D=0.5) allowed us to test the reliability of the CFD, the result were compared with those of experimental literature, a very good concordance was observed. The stream function, the velocity profile, the velocity fields and power number are analyzed. It was shown that the hydrodynamics is modified by the curvature of the mobile which plays a key role.

Keywords: agitated tanks, curved blade agitator, laminar flow, CFD modelling

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Authors: Bouafia-Chergui Souâd, Chabani Malika, Bensmaili Aicha

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Water treatment and especially, medicament pollutants are nowadays important problems. Degradation of oxytetracycline was carried out using combined process of low-frequency ultrasound (US), ultraviolet irradiation and a catalyst. The effectiveness of the coupled processes has been evaluated by studying the effects of various operating parameters including initial OTC concentration, solution pH and catalyst mass. For the photolysis process, the monochromatic ultraviolet light wavelength utilized was 365 nm. The sonolysis experiments were performed with ultrasound at a frequency of 40 kHz. The heterogeneous photocatalysis was studied in the presence of TiO2. The processes were employed individually, and simultaneously to examine the details of the processes and to investigate the contribution of each process. Low UV intensity (12W), low pH and high mass of TiO2 conditions enhanced the sono-photocatalytic degradation of OTC. The results showed that the individual contribution sonochemical and photochemical reactions are very low, however, their coupling increases the degradation rate of 8 times compared to photolysis and 2 times compared to sonolysis. There is a synergistic effect between the two modes of radiation, UV and U.S. leading to 82.04% degradation yield. An application of these combined processes on the treatment of a real pharmaceutical wastewater was examined.

Keywords: sonolysis, photocatalysis, combined process, antibiotic

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Authors: Thi Huong Vu, Haelee Fenton, Thi Huong Tra Nguyen, Gary Dykes

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In the present study, a submerged fermentation of carob kibble with Saccharomyces cerevisiae (S. cerevisiae) was performed. The total phenolic content and antioxidant activity in fermented carob kibble were determined by Folin–Ciocalteu method and scavenging capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The study showed that S. cerevisiae improved total phenolic content by 45 % and 50 % in acetone and water extracts respectively. Similarly, the antioxidant capacity of water extracts increased by 25 % and 41%, while acetone extracts indicated by 70% and 80% in DPPH and ABTS respectively. It is also found that initial pH 7.0 was more effective in improvement of total phenolic content and antioxidant activity. The efficiency of treatment was recorded at 15 h. This report suggested that submerged fermentation with S. cerevisiae is a potential and cost effective manner to further increase bioactive compounds in carob kibble, which are in use for food, cosmetic and pharmaceutical industries.

Keywords: antioxidant activity, carob kibble, saccharomyces cerevisiae, submerged fermentation, total phenolics

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Authors: Hoda Dehghani, Zahra Dehghani

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Considering the obvious growth and variety of veterinary biological product and increase consumption and also the price, it is necessary to establish the rules and serious monitoring of this products which are less expensive than the original products. The scope of this research is the study of comparing the registration criteria and procedures of veterinary biological drugs in the world's leading agencies such as EMA, FDA, and WHO. For this, purpose the rules and regulations for registration of these drugs in prestigious organizations such as the FDA, EMA and WHO were examined and compared with the existing legislation in Iran. Studies show that EMA is the forefront of the compilation and registration of drugs in the world. China is a one of the greatest country in the development of drugs and establishes very closely guidelines with creditable global guidelines, and Now, is the first country to implement the rules codified in the Far East and followed by china, India and, South Korea and Taiwan have taken incorporate the industry's top ranking in Asia. At now, Asia by creating appropriate indicators not only as a powerful center in the field of drug delivery but also as a competitor to the United States is a major source of drug discovery and creation of innovation. the activities such as clinical trials and pharmaceutical investment is the speed of technology on the continent.

Keywords: veterinary biological product, regulation of registration, biological products, regularity authorities

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Authors: Ihsan Burak Cam, Ferhan Balci-Torun, Ayhan Topuz, Esin Ari, Ismail Gokhan Deniz, Ilker Genc

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The seeds of Vaccaria hispanica have been used in food and pharmaceutical industry. It is an important product due to its superior starch granules, triterpenic saponins, and cyclopeptides suitable for drug delivery. V. hispanica naturally grows in different climatic regions and has genotypes that differ in terms of seed content and composition. Sixty-six V. hispanica seed specimens were collected based on the representation of the distribution in all regions of Turkey and the determination of possible genotypic differences between regions. The seeds, collected from each of the 66 locations, were grown in greenhouse conditions in Akdeniz University, Antalya. Saponin and cyclopeptide contents of the V. hispanica seeds were determined after harvest. Accelerated solvent extraction (ASE) was applied for the extraction of saponins and cyclopeptides. Cyclopeptide (segetalin A) and saponin content of V. hispanica seeds were found in the range of 0.165-0.654 g/100 g and 0.15-1.14 g/100 g, respectively. The results were found to be promising for the seeds from Turkey in terms of saponin content and quality. Acknowledgment: This study was supported by the Scientific and Research Council of Turkey (TUBITAK) (project no 112 O 136).

Keywords: Vaccaria hispanica, saponin, cyclopeptid, cow cockle seeds

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Authors: Jorge A. Ruiz-Vanoye, Ocotlán Díaz-Parra, Alejandro Fuentes-Penna, José J. Hernández-Flores, Edith Olaco Garcia

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The Project Scheduling Problem (PSP) is a generic name given to a whole class of problems in which the best form, time, resources and costs for project scheduling are necessary. The PSP is an application area related to the project management. This paper aims at being a guide to understand PSP by presenting a survey of the general parameters of PSP: the Resources (those elements that realize the activities of a project), and the Activities (set of operations or own tasks of a person or organization); the mathematical models of the main variants of PSP and the algorithms used to solve the variants of the PSP. The project scheduling is an important task in project management. This paper contains mathematical models, resources, activities, and algorithms of project scheduling problems. The project scheduling problem has attracted researchers of the automotive industry, steel manufacturer, medical research, pharmaceutical research, telecommunication, industry, aviation industry, development of the software, manufacturing management, innovation and technology management, construction industry, government project management, financial services, machine scheduling, transportation management, and others. The project managers need to finish a project with the minimum cost and the maximum quality.

Keywords: PSP, Combinatorial Optimization Problems, Project Management; Manufacturing Management, Technology Management.

Procedia PDF Downloads 389

Authors: Afaf Bouchoucha, Karima Si Larbi, Mohamed Amine Bourouaia, Salah.Boulanouar, Safia.Djabbar

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The synthesis, characterization and comparative biological study of manganese (II) and copper (II) complexes with an heterocyclic ligand used in pharmaceutical field (Scheme 1), were reported. Two kinds of complexes were obtained with derivative sulfonamide, [M (L)₂ (H₂O)₂].H₂O and [M (L)₂ (Cl)₂]3H₂O. These complexes have been prepared and characterized by elemental analysis, FAB mass, ESR magnetic measurements, FTIR, UV-Visible spectra and conductivity. Their stability constants have been determined by potentiometric methods in a water-ethanol (90:10 v/v) mixture at a 0.2 mol l-1 ionic strength (NaCl) and at 25.0 ± 0.1 ºC using Sirko program. DFT calculations were done using B3LYP/6-31G(d) and B3LYP/LanL2DZ. The antimicrobial activity of ligand and complexes against the species Escherichia coli, P. aeruginosa, Klebsiella pneumoniae, S. aureus, Bacillus subtilisan, Candida albicans, Candida tropicalis, Saccharomyces, Aspergillus fumigatus and Aspergillus terreus has been carried out and compared using agar-diffusion method. Also, the toxicity study was evaluated on synchesis complexes using Mice of NMRI strain.

Keywords: hetterocyclic ligand, complex, stability constant, antimicrobial activity, DFT, acute and genotoxicity study

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Authors: Mhuji Kilonzo

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Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

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Authors: N. Zanganeh, M. Zabet

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Lactulose is a synthetic disaccharide which has remarkable applications in food and pharmaceutical fields. Lactulose is not found in nature and it is produced by isomerization reaction of lactose in an alkaline environment. It should be noted that this reaction has a very low yield since significant amount of lactose stays un-reacted in the system. Basically, purification of lactulose is difficult and costly. Previous studies have revealed that solubility of lactose and lactulose are significantly different in ethanol. Considering the fact that solubility is also affected by temperature itself, we investigated the effect of ethanol and temperature on separation process of lactose from the syrup containing lactose and lactulose. For this purpose, a saturated solution containing lactulose and lactose was made at three different temperatures; 25⁰C (room temperature), 31⁰C, and 37⁰C first.  Five samples containing 2g saturated solution was taken and then 2g, 3g, 4g, 5g, and 6g ethanol separately was added to the sampling tubes. Sampling tubes were kept at respective temperatures afterward. The concentration of lactose and lactulose after separation process measured and analyzed by High Performance Liquid Chromatography (HPLC). Results showed that ethanol has such a greater impact than operating temperature on purification process. Also, it was observed that the maximum rate of separation occurred at initial amount of added ethanol.

Keywords: lactulose, lactose, purification, solubility

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Authors: Sanjaykumar R. Patel, Parth R. Kayastha

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α-lactose monohydrate is widely used in the pharmaceutical industries as an inactive substance that acts as a vehicle or a medium for a drug or other active substance. It is a byproduct of dairy industries, and the recovery of lactose from whey not only boosts the improvement of the economics of whey utilization but also causes a reduction in pollution as lactose recovery can reduce the BOD of whey by more than 80%. In the present study, levels of process parameters were kept as initial lactose concentration (30-50% w/w), sonication amplitude (20-40%), sonication time (2-6 hours), and crystallization temperature (10-20 ^oC) for the recovery of lactose in ultrasound assisted cooling crystallization. In comparison with cooling crystallization, the use of ultrasound enhanced the lactose recovery by 39.17% (w/w). The parameters were optimized for the lactose recovery using Taguchi Method. The optimum conditions found were initial lactose concentration at level 3 (50% w/w), amplitude of sonication at level 2 (40%), the sonication time at level 3 (6 hours), and crystallization temperature at level 1 (10 °C). The maximum recovery was found to be 85.85% at the optimum conditions. Sonication time and the initial lactose concentration were found to be significant parameters for the lactose recovery.

Keywords: crystallization, lactose, Taguchi method, ultrasound

Procedia PDF Downloads 181

Authors: He Yuhai, Ahmad Ziad Bin Sulaiman

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Tongkat Ali, or Eurycoma longifolia, is a traditional Malay and Orang Asli herb used as aphrodisiac, general tonic, anti-Malaria, and anti-Pyretic. It has been recognized as a cashcrop by Malaysia due to its high value for the pharmaceutical use. In Tongkat Ali, eurycomanone, a quassinoid is usually chosen as a marker phytochemical as it is the most abundant phytochemical. In this research, ultrasound and enzyme were used to enhance the extraction of Eurycomanone from Tongkat Ali. Ultrasonic assisted extraction (USE) enhances extraction by facilitating the swelling and hydration of the plant material, enlarging the plant pores, breaking the plant cell, reducing the plant particle size and creating cavitation bubbles that enhance mass transfer in both the washing and diffusion phase of extraction. Enzyme hydrolyses the cell wall of the plant, loosening the structure of the cell wall, releasing more phytochemicals from the plant cell, enhancing the productivity of the extraction. Possible effects of ultrasound on the activity of the enzyme during the hydrolysis of the cell wall is under the investigation by this research. The extracts was analysed by high performance liquid chromatography for the yields of Eurycomanone. In this whole process, the conventional water extraction was used as a control of comparing the performance of the ultrasound and enzyme assisted extraction.

Keywords: ultrasound, enzymatic, extraction, Eurycoma longifolia

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Authors: Niranjan Mukherjee, Burga Braun, Ulrich Szewzyk

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Recalcitrant pharmaceuticals are increasingly found in urban water systems forced by demographic changes. The groundwater-surface water interface, or the hyporheic zone, is known for its impressive self-purification capacity of water bodies. Redox gradients present in this zone provide a wide range of electron acceptors and harbour diverse microbial communities. Biotic transformations of pharmaceuticals in this zone have been demonstrated, but not much information is available on the kind of communities bringing about these transformations. Therefore, bioreactors using sediment from the hyporheic zone of a river in Berlin were set up and fed with iopromide, a recalcitrant iodinated X-ray contrast medium. Iopromide, who’s many oxic and anoxic transformation products have been characterized, was shown to be transformed in such a bioreactor as it passes along the gradient. Many deiodinated transformation products of iopromide could be identified at the outlet of the reactor. In our experiments, it was seen that at the same depths of the column, the transformation of iopromide increased over time. This could be an indication of the microbial communities in the sediment adapting to iopromide. The hyporheic zone, with its varying redox conditions, mainly due to the upwelling and downwelling of surface and groundwater levels, could potentially provide microorganisms with conditions for the complete transformation of recalcitrant pharmaceuticals.

Keywords: iopromide, hyporheic zone, recalcitrant pharmaceutical, redox gradients

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Authors: A. Shashank Tiwari, S. P. Mahapatra

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Scale-up is defined as the process of increasing batch size. Scale-up of a process viewed as a procedure for applying the same process to different output volumes. There is a subtle difference between these two definitions: batch size enlargement does not always translate into a size increase of the processing volume. In mixing applications, scale-up is indeed concerned with increasing the linear dimensions from the laboratory to the plant size. On the other hand, processes exist (e.g., tableting) where the term ‘scale-up’ simply means enlarging the output by increasing the speed. To complete the picture, one should point out special procedures where an increase of the scale is counterproductive and ‘scale-down’ is required to improve the quality of the product. In moving from Research and Development (R&D) to production scale, it is sometimes essential to have an intermediate batch scale. This is achieved at the so-called pilot scale, which is defined as the manufacturing of drug product by a procedure fully representative of and simulating that used for full manufacturing scale. This scale also makes it possible to produce enough products for clinical testing and to manufacture samples for marketing. However, inserting an intermediate step between R&D and production scales does not, in itself, guarantee a smooth transition. A well-defined process may generate a perfect product both in the laboratory and the pilot plant and then fail quality assurance tests in production.

Keywords: scale up, research, size, batch

Procedia PDF Downloads 377

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

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The complexes of transition metals with various organic ligands have been extensively studied as models of some important pharmaceutical molecules. It was found that biological properties of different substituted organic molecules are improved when they are complexed by different metals. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In the present work, we have bioassayed the antibacterial potency of benzimidazoles and their metal salts (Cu or Zn) against yeast Sarcina lutea. In order to validate our in vitro study, we performed in silico studies using molecular docking software. The investigated compounds and their metal complexes (Cu, Zn) showed good to moderate inhibitory activity against Sarcina lutea. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and improved antibacterial activity in comparison with non-complexed ligands. These results are part of the CMST COST Action No. 1105 "Functional metal complexes that bind to biomolecules".

Keywords: organometallic complexes, benzimidazoles, chemometric design, Sarcina lutea

Procedia PDF Downloads 308

Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed

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Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18–23). Then, their anticonvulsant activity was evaluated using a pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18–23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy, with compound 23 being the best. Interestingly, most of the synthesized molecules showed a reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.

Keywords: isatin and adamantane, anticonvulsant activity, PTZ-induced seizure, molecular docking

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Authors: Mont Kumpugdee-Vollrath, Khaled Abdallah

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Liposomes and pegylated liposomes were widely used as drug delivery system in pharmaceutical field since a long time. However, in the former time, polyethylene glycol (PEG) was connected into phospholipid after the liposomes were already prepared. In this paper, we intend to study the possibility of applying phospholipids which already connected with PEG and then they were used to prepare liposomes. The model drug resveratrol was used because it can be applied against different diseases. Cholesterol was applied to stabilize the membrane of liposomes. The thin film technique in a laboratory scale was a preparation method. The liposomes were then characterized by nanoparticle tracking analysis (NTA), photon correlation spectroscopy (PCS) and light microscopic techniques. The stable liposomes can be produced and the particle sizes after filtration were in nanometers. The 2- and 3-chains-PEG-phospholipid (PL) caused in smaller particle size than the 4-chains-PEG-PL. Liposomes from PL 90G and cholesterol were stable during storage at 8 °C of 56 days because the particle sizes measured by PCS were almost not changed. There was almost no leakage of resveratrol from liposomes PL 90G with cholesterol after diffusion test in dialysis tube for 28 days. All liposomes showed the sustained release during measuring time of 270 min. The maximum release amount of 16-20% was detected with liposomes from 2- and 3-chains-PEG-PL. The other liposomes gave max. release amount of resveratrol only of 10%. The release kinetic can be explained by Korsmeyer-Peppas equation. 

Keywords: liposome, NTA, resveratrol, pegylation, cholesterol

Procedia PDF Downloads 143