FORMUALTION AND DEVELOPMENT OF MUCOADHESIVE SUSTAINED RELEASE BUCCAL TABLETS AND PATCHES OF 5-FLUOROURACIL USING DIFFERENT POLYMERS

 Objective: The present research study was undertaken to formulate mucoadhesive sustained release buccal tablets and patches of 5-fluorouracil (5-FU).Method: For the research experiment work design expert software version 10, stat-ease, Inc. has been used. A 32 full factorial design was selected for the formulation of the buccal tablet as well as buccal patches. In this research work, formulated tablets and patches using different polymers such as carbopol 974p, polyvinylpyrrolidone-K 30, sodium deoxycholate, microcrystalline cellulose, and polyvinyl alcohol. An after formulation of batches formulated products studied for characterization, namely, Fourier transform infrared (FTIR) and differential scanning calorimeter (DSC). Evaluation parameters studied such as weight uniformity, thickness, hardness, friability, and content uniformity also carried out. For drug release purpose from the formulation of buccal tablet and patches in vitro drug released performed. In vivo drug releases study also carried out using Rabbit for drug reaction point of view.Results: Design expert showed the significant results on independent and dependent variables. The R-Squared 0.9943 for drug release and 0.9985 for swelling index is in reasonable agreement with the formulations. FTIR and DSC indicating compatibility of the drug and polymers in the tablet formulation and patch formulations at the molecular level. The drug release of buccal tablet showed 75.10–99.34% and buccal patches showed 58.41–81.43%. These formulations showed good results when compared to the conventional tablet.Conclusion: Formulation of mucoadhesive sustained release buccal tablets and patches of 5-FU successfully done using different polymers, which would definitely help in increasing bioavailability of the drug

DEVELOPMENT OF NEW PYRAZOLE HYBRIDS AS ANTITUBERCULAR AGENTS: SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY

Objective: synthesis of new 1, 3-diphenyl pyrazole derivatives 9(a-f) and 10(a-f) using molecular hybridization approach for antitubercular and cytotoxic studies.Methods: The structures of synthesized compounds were confirmed by 1H-NMR, 13C-NMR and mass spectra's. The antitubercular activity of compounds and standard drugs were assessed against Mycobacterium tuberculosis using microplate Alamar Blue assay (MABA).  The cytotoxic activities were performed by Sulforhodamine B (SRB) assay. The molecular docking and in silico ADME prediction were studied by using Schrodinger.Results: The results reveals that the compounds 9c, 9d, 10c and 10d exhibited substantial antitubercular potential with MIC < 20 μM. The cytotoxic studies revealed that the active compounds (9d, 10a, and 10d) are non-toxic to HeLa cancer cell lines with selectivity index >10. The molecular docking study was performed to study the binding orientation and affinity of synthesized compounds for InhA enzyme.Conclusion: The study explored that the 1, 3-diphenyl pyrazole hybrids coupled with well known antitubercular drugs could be a potential lead for antitubercular agents. In-silico molecular docking study helps to identify their corresponding intermolecular ligand-protein interactions with target enzyme. Also ADME prediction studies revealed that the compounds were in acceptable range to have pharmacokinetic parameters

Efficient one-pot synthesis, molecular docking and in silico ADME prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents

Bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4-hydroxycoumarin and substituted aromatic aldehydes using succinimide-N-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of Leishmania donovani. Compounds 3a (IC50= 155 μg/mL), 3g (IC50= 157.5 μg/mL) and 3l (IC50= 150 μg/mL) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50= 490 μg/mL). Also, synthesized compounds 3(a-l) did not show cytotoxicity against HeLa cell line upto tested concentrations. Further, molecular docking study against Adenine phosphoribosyltransferase of Leishmania donovani showed good binding interactions. ADME properties were analyzed and showed good oral drug candidate like properties. The synthesized compounds were also shown good drug likeness and drug score values when compared with drugs currently used in therapy. The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent

Ultrasound-promoted One-Pot, Three Component Synthesis Of Novel 5-Amino-2-(4-Chlorophenyl)-7- Substituted Phenyl-8,8a-Dihydro-7H-[1,3,4]Thiadiazolo[3,2-A]Pyrimidine-6-Carbonitrile Derivatives

The 19th International Electronic Conference on Synthetic Organic Chemistry session General Organic SynthesisHere is the report of an environment friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7- substituted phenyl-8,8a-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carbonitrile derivatives. Multi-component reactions are useful for the creation of chemical libraries of drug-like compounds with levels of molecular complexity and diversity. 1,3,4-Thiadiazolo[3,2-a]pyrimidine skeleton belongs to a well-known and important class of fused heterocycles prevalent in a number of natural products of biological activities including antitumor, fungicidal, antibacterial, and herbicidal, hence, prompted us to synthesis 1,3,4-Thiadiazolo[3,2-a]pyrimidines. The final ten derivatives were obtained in excellent yield through a one-pot, three component condensation reaction of aldehyde, 4-chlorophenyl-2-aminothiadiazole, and malononitrile in 10-12 ml of ethanol as solvent and sodium hydroxide as a catalyst. (VCX 500-220, Ultrasound Solid probe, irradiation at 800C and 20% amplitude). We have carried out the same reaction by conventional method, which requires 9-10 hrs of refluxing and yield is lesser. Because of the advantage of faster reaction rates and better yields, use of Ultrasound solid probe, was found to be more suitable for this reaction. Structure of the synthesized derivatives was confirmed by IR, NMR and Mass spectral stud

TASTE MASKING OF DONEPEZIL HYDROCHLORIDE USING DIFFERENT ION EXCHANGE RESINS- A COMPARATIVE STUDY

Taste mainly depends on the physiology, sensitivity and structure of taste buds. It is an important parameter in administering drugs orally. Bitter taste is a major limitation to patient compliance. Donepezil hydrochloride (DH) is a bitter drug used in Alzheimer's disease. Amongst the many techniques for taste masking, using ion exchange resins has been extensively reported. The technique of forming tasteless complexes with bitter drugs involves selection of most appropriate exchanger and optimization of complexing ratio. The aim of the present work was to select the best cationic exchanger amongst Indion 414, Indion 234 and Indion 214. All parameters were optimized to produce drug-loaded tasteless complexes. Complexation was carried out using batch process prior to which, acid-alkali activation was performed to remove adsorbed impurities from the resin bed surface and hence improve loading efficiency. UV-spectrophotometric method was used to determine percent drug loading. The molecular properties of drug resin complexes were studied using Fourier Transform Infra-red Spectroscopy, Differential Scanning Calorimetry and Xray Powder Diffraction which confirmed complexation. Indion 414 was found to give highest drug loading and minimal drug was released from the complex at salivary pH. Key words: Donepezil HCl, Ion exchange resins, Molecular properties, Taste maskin

Oil Price Shock and its Impact on the Macroeconomic Variables of Pakistan: A Structural Vector Autoregressive Approach

This study examines the dynamic effects of the oil price shocks on the key macroeconomic variables of Pakistan. A Structural Vector Autoregressive model is used on yearly data from 1960 to 2014. The impulse response functions indicate that the oil price shocks depress the real gross domestic product while the real exchange rate also experiences depreciation. However, the long-term interest rate and the inflation rate rise as a result of a positive oil price shock. The unanticipated changes in these macroeconomic variables threaten the economic stability of Pakistan; specifically, higher inflation and interest rates hamper the economy's growth rate. Lastly, the variance decomposition analysis illustrates that the oil price shocks have the most impact on the inflation rate of Pakistan. Keywords: SVAR; Oil Price Shocks; Macroeconomic Variable JEL Classifications: C22; E40; E31; E50; Q43

TASTE MASKING OF DONEPEZIL HYDROCHLORIDE USING DIFFERENT ION EXCHANGE RESINS- A COMPARATIVE STUDY

Taste mainly depends on the physiology, sensitivity and structure of taste buds. It is an important parameter in administering drugs orally. Bitter taste is a major limitation to patient compliance. Donepezil hydrochloride (DH) is a bitter drug used in Alzheimer's disease. Amongst the many techniques for taste masking, using ion exchange resins has been extensively reported. The technique of forming tasteless complexes with bitter drugs involves selection of most appropriate exchanger and optimization of complexing ratio. The aim of the present work was to select the best cationic exchanger amongst Indion 414, Indion 234 and Indion 214. All parameters were optimized to produce drug-loaded tasteless complexes. Complexation was carried out using batch process prior to which, acid-alkali activation was performed to remove adsorbed impurities from the resin bed surface and hence improve loading efficiency. UV-spectrophotometric method was used to determine percent drug loading. The molecular properties of drug resin complexes were studied using Fourier Transform Infra-red Spectroscopy, Differential Scanning Calorimetry and Xray Powder Diffraction which confirmed complexation. Indion 414 was found to give highest drug loading and minimal drug was released from the complex at salivary pH

R&D intensity, knowledge creation process and new product performance: the mediating role of international R&D teams

Although previous studies have shown the positive effect of research and development (R&D) intensity on new product performance (NPP), our understanding about the mechanisms through which R&D intensity influence NPP is less understood. In this paper, we focus on the mediating role of international R&D teams in explaining the effect of R&D intensity on NPP. Since R&D teams are dispersed across the globe, thus examining the role of international R&D teams will provide a more nuanced understanding of the mechanisms through which R&D intensity contributes to NPP. Using survey data from 201 Ghanaian firms engaged in internationalisation activities, the results suggest that the use of international R&D teams mediates the relationship between R&D intensity and NPP. Moreover, the findings indicate that the use of international R&D teams improves NPP and that this linkage is amplified when the knowledge creation process inside the firm is stronger. We discuss the implications of these findings for theory and practice

E2-MACH: Energy Efficient Multi-Attribute Based Clustering Scheme for Energy Harvesting Wireless Sensor Networks

Internet of things have emerged enough due to its applications in a wide range of fields such as governance, industry, healthcare, and smart environments (home, smart, cities, and so on). Internet of things–based networks connect smart devices ubiquitously. In such scenario, the role of wireless sensor networks becomes vital in order to enhance the ubiquity of the Internet of things devices with lower cost and easy deployment. The sensor nodes are limited in terms of energy storage, processing, and data storage capabilities, while their radio frequencies are very sensitive to noise and interference. These factors consequently threaten the energy consumption, lifetime, and throughput of network. One way to cope with energy consumption issue is energy harvesting techniques used in wireless sensor network–based Internet of things. However, some recent studies addressed the problems of clustering and routing in energy harvesting wireless sensor networks which either concentrate on energy efficiency or quality of service. There is a need of an adequate approach that can perform efficiently in terms of energy utilization as well as to ensure the quality of service. In this article, a novel protocol named energy-efficient multi-attribute-based clustering scheme (E2-MACH) is proposed which addresses the energy efficiency and communication reliability. It uses selection criteria of reliable cluster head based on a weighted function defined by multiple attributes such as link statistics, neighborhood density, current residual energy, and the rate of energy harvesting of nodes. The consideration of such parameters in cluster head selection helps to preserve the node’s energy and reduce its consumption by sending data over links possessing better signal-to-noise ratio and hence ensure minimum packet loss. The minimized packet loss ratio contributes toward enhanced network throughput, energy consumption, and lifetime with better service availability for Internet of things applications. A set of experiments using network simulator 2 revealed that our proposed approach outperforms the state-of-the-art low-energy adaptive clustering hierarchy and other recent protocols in terms of first-node death, overall energy consumption, and network throughput