ENHANCEMENT OF DISSOLUTION AND STABILITY OF CANDESARTAN CILEXETIL–LOADED SILICA POLYMERS

Objective: To prepare stable amorphous solid dispersions of candesartan cilexetil (CAN) with different types of silica, including non-porous (aerosil 200) and porous silica (sylysia 350) using the spray-drying method. Methods: various ratios of candesartan cilexetil (CAN) were spray dried with aerosil and sylysia. Powder x-ray diffraction (x-ray) differential scanning calorimetry (DSC), SEM were used to characterize the spray dried powders in addition to dissolution and stability studies. Results: X-ray results showed that the spray–dried (CAN) in the prepared solid dispersion were in amorphous form irrespective of the used silica. In (DSC) analysis, the melting peak of spray-dried (CAN-silica) solid dispersion disappeared. Dissolution property of (CAN) was remarkably improved by formulating with silica particles. In comparing the effect of the type of the silica particles, the dissolution rate of (CAN) from the spray-dried (CAN-sylysia) was faster than that (CAN-aerosil 200) irrespective of the drug content. It was also shown that the spray-dried formulation with silica did not recrystallize when storing at severe storage conditions (40 °C, 75% RH) for three months, while spray-dried (CAN) without silica easily re-crystallized under the same conditions. Conclusion: Spray drying of (CAN) with sylysia 350 is an efficient method to enhance the dissolution and stability of the drug

Applications of blockchain technology in sustainable manufacturing and supply chain management: A systematic review

Developing sustainable products and processes is essential for the survival of manufacturers in the current competitive market and the industry 4.0 era. The activities of manufacturers and their supply chain partners should be aligned with sustainable development goals. Manufacturers have faced many barriers and challenges in implementing sustainable practices along the entire supply chain due to globalisation, outsourcing, and offshoring. Blockchain technology has the potential to address the challenges of sustainability. This study aims to explain the applications of blockchain technology to sustainable manufacturing. We conducted a systematic literature review and explained the potential contributions of blockchain technology to the economic, environmental, and social performances of manufacturers and their supply chains. The findings of the study extend our understanding of the blockchain applications in sustainable manufacturing and sustainable supply chains. Furthermore, the study explains how blockchain can influence the sustainable performance of manufacturers by creating transparency, traceability, real-time information sharing, and security of the data capabilities

Multiple Targeting Approaches on Histamine H-3 Receptor Antagonists

With the very recent market approval of pitolisant (Wakix (R)), the interest in clinical applications of novel multifunctional histamine H-3 receptor antagonists has clearly increased. Since histamine H-3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H-3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures

Green synthesized extracts/Au complex of <i>Phyllospongia lamellosa</i>:unrevealing the anti-cancer and anti-bacterial potentialities, supported by metabolomics and molecular modeling

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV–vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads

New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes

Saccharomonospora sp. UR22 and Dietzia sp. UR66, two actinomycetes derived from the Red Sea sponge Callyspongia siphonella, were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A (1), a novel brominated oxo-indole alkaloid, convolutamydine F (2) along with other three known induced metabolites (3-5) were isolated from the EtOAc extract of Saccharomonospora sp. UR22 and Dietzia sp. UR66 co-culture. Additionally, axenic culture of Saccharomonospora sp. UR22 led to isolation of six known microbial metabolites (6-11). A kinase inhibition assay results showed that compounds 1 and 3 were potent Pim-1 kinase inhibitors with an IC50 value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds 1 and 3 in the ATP pocket of Pim-1 kinase. Testing of compounds 1 and 3 displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 2.8 and 4.2 μM, respectively). These results suggested that compounds 1 and 3 act as potential Pim-1 kinase inhibitors that mediate the tumor cell growth inhibitory effect. This study highlighted the co-cultivation approach as an effective strategy to increase the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes

Low Cost Lab on Chip for the Colorimetric Detection of Nitrate in Mineral Water Products

The diagnostics of health status and the quality of drinking water are among the most important United Nations sustainable development goals. However, in certain areas, wars and instability have left millions of people setting in refugee camps and dangerous regions where infrastructures are lacking and rapid diagnostics of water quality and medical status are critical. In this work, microfluidic testing chips and photometric setups are developed in cheap and portable way to detect nitrate concentrations in water. The performed test is designed to work according to the Griess procedure. Moreover, to make it simple and usable in areas of low resource settings, commercially available Arduino mega and liquid crystal display (LCD) shield are utilized to process and display results, respectively. For evaluation purposes, different local products of tap water, bottled drinking water, and home-filter treated water samples were tested using the developed setup. A calibration curve with coefficient of determination (R2) of 0.98 was obtained when absorbance of the prepared standard solutions was measured as a function of the concentrations. In conclusion, this is the first step towards a compact, portable, and reliable system for nitrate detection in water for point-of-care applications

Molybdenum-modified platinum electrodes

The modification of Pt electrodes with Mo compounds improves their catalytic activity toward the oxidation of methanol and formaldehyde in acidic solutions. The two sets of Mo oxides that have been studied in this work are the Hydrogen Molybdenum Bronze, HₓMoO₃, 0<x<2, and the Molybdenum Oxides, MoOₓ, 2<x<3. -- It has been found that the bronze (H₂MoO₃)ads is generated at the Pt surface in an in situ fashion upon the application of potentials more negative than 0 vs. Ag/AgCl. At higher positive potentials, the adsorbed bronze is oxidized to several intermediates that interact with methanol and facilitate its oxidation on the Pt surface. The nature of the interaction between the adsorbed intermediates and methanol needs further experimental investigation. -- The deposition of MoO₃ on the surface of a commercial carbon supported Pt catalyst, has been achieved. The catalytic promotion observed with the modified catalyst over its unmodified counterpart has been explained in terms of the bi-functional mechanism introduced by Watanabe and Motoo. The activity of the Mo modified catalyst increases with the elevation of the MoO₃ surface concentration to a certain limit, then it decreases with further Mo addition. The extra MoO₃ content shields the Pt sites from the methanol or the formaldehyde molecules. In addition, it is added at the expense of the carbon content of the catalyst that is required for the electronic conductivity through the modified electrode

Lengths in semi-free groups

Lyndon [3] introduced the idea of a length function on a group in order to give a free product structure for the group in terms of the length function. Work has been done on length functions by Harrison [1], Hoare [2] and others with the objective of studying the structure of groups equipped with length functions