Stereoselective synthesis and X-ray structure determination of novel 1,2-dihydroquinolinehydrazonopropanoate derivatives

A novel series of 1,2-dihydroquinolinhydrazonopropanoate have been synthesized via a convenient aza-Michael addition reaction between hydrazinylquinolinones and ethyl propiolate in ethanol under refluxing temperature. The structures for all obtained products were confirmed with FTIR, NMR spectrums, as well as mass spectrometry. In addition, the monoclinic structure for compounds 8a, 8c, and 8d was also confirmed via X-ray crystallography analyses. The E-configuration for the obtained products was confirmed form the X-ray analysis. On the other hand, the crystal packing shows that the intermolecular and hydrogen bonds between atoms are parallel to the bc plan

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets

The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15 ± 4.2 μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p < 0.05, ANOVA/Tukey) lower release of IND 13.70 ± 1.6 and 56.46 ± 3.8% compared with 1:1 (89.61 ± 2.5, 80.13 ± 2.6%) and 1:0.5 (39.46 ± 0.9 & 43.38 ± 3.12) after 3 and 43 h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95 ± 0.68 × 10−6cm/s compared to free IND 23.06 ± 3.56 × 10−6cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit

Azides in the Synthesis of Various Heterocycles

In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal, catalyzed, or noncatalyzed reaction conditions. The aforementioned reactions in the aim to prepare basic five-, six-, organometallic heterocyclic-membered systems and/or their fused analogs. This review article also provides a report on the developed methods describing the synthesis of various heterocycles from organic azides, especially those reported in recent papers (till 2020). At the outset, this review groups the synthetic methods of organic azides into different categories. Secondly, the review deals with the functionality of the azido group in chemical reactions. This is followed by a major section on the following: (1) the synthetic tools of various heterocycles from the corresponding organic azides by one-pot domino reaction; (2) the utility of the chosen catalysts in the chemoselectivity favoring C−H and C-N bonds; (3) one-pot procedures (i.e., Ugi four-component reaction); (4) nucleophilic addition, such as Aza-Michael addition; (5) cycloaddition reactions, such as [3+2] cycloaddition; (6) mixed addition/cyclization/oxygen; and (7) insertion reaction of C-H amination. The review also includes the synthetic procedures of fused heterocycles, such as quinazoline derivatives and organometal heterocycles (i.e., phosphorus-, boron- and aluminum-containing heterocycles). Due to many references that have dealt with the reactions of azides in heterocyclic synthesis (currently more than 32,000), we selected according to generality and timeliness. This is considered a recent review that focuses on selected interesting examples of various heterocycles from the mechanistic aspects of organic azides

Effects of sand and gating architecture on the performance of foot valve lever casting components used in pump industries

Funding Information: The authors thank Kalasalingam Academy of Research and Education, Krishnankoil for providing the facilities for various tests and characterizations. The King Saud University authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project no. RG-148. This Research was funded by King Mongkut's University of Technology North Bangkok has received funding support from the National Science, Research and Innovation Fund (NSRF) (Grant No. KMUTNB-MHESI-64-16.1). Publisher Copyright: © 2021 The Author(s)This work addresses manufacture, testing and simulation of foot valve lever (FVL) for monoblock pump industry, using a cost-effective casting design process. The impact of different types of sands, such as air-set, dry and sodium silicate as well as gating designs, namely H-, U- and O-type, were studied with respect to surface roughness and porosity. The mold pattern was produced using additive manufacturing (AM) technology. Both experimental and numerical investigations were performed on the temperature distribution of molten metal at random locations for the different gating configurations or designs, considering mold filling and solidification. It was evident from the experimental investigation that contribution of air-set sand and O-type gating architecture showed limited consistency effects. Importantly, gating architecture was the most influential parameter to determine all specified quality outcomes, independent of sand mold. An order of O < H < U-type was obtained from the gating designs for minimal surface roughness and percentage of porosity. Furthermore, the microstructure analysis depicted only an irregular defect with minimum quantity at both surface and cross-section of O-type at two different locations. Optimum pouring temperatures of 740, 750 and 790 °C were obtained for mold filling of all 24 components of H-, O- and U-type of gating designs, respectively. The varying solidification temperature was observed from real time thermocouple reading, which was in close agreement with the numerical simulation. Evidently, O-type of gating design exhibited best performance for large-scale development of the FVL in terms of surface roughness, porosity and cooling effects.Peer reviewe

Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors

Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14) could have a potential interest in delivery of anti-cancer agents to tumor cells. Attachment of SST to different nano-carriers e.g., polymeric nanoparticles is limited due to the difficulty of interaction between SST itself and those nano-carriers. Furthermore, the instability problems associated with the final formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive and negative charge of SST and citrate-AuNPs could be considered a new technique to get stable non-aggregated AuNPs coated with SST. Different analyses techniques have been performed to proof the principle of coating between AuNPs and SST. Furthermore, cellular uptake study on HCC-1809 cell lines has been investigated to show the ability of AuNPs coated SST to enter the cells via SST receptors. Dynamic light scattering (DLS) indicated a successful coating of SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of AuNPs with SST. Cellular uptake study on HCC-1806 cell lines showed that the number of AuNPs-SST per cell is significantly higher compared to citrate-AuNPs when quantified using inductively coupled plasma spectroscopy. Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor-specific binding. In conclusion, AuNPs could be attached to SST via adsorption to get stable AuNPs coated SST. This new formulation has a potential to target SST receptors localized in many normal and tumor cells

Dissolution Enhancement and Formulation of Rapid-Release Lornoxicam Mini-Tablets

The aim was to enhance the dissolution of lornoxicam (LOR) and to produce mini-tablets with an optimised system to provide a rapid-release multi-particulate formulation. LOR systems were prepared through co-evaporation with either polyethylene glycol 6000 or Pluronic® F-68 (PLU) and adsorption onto Neusilin® US2 alone or co-adsorption in the presence of different amounts of polysorbate 80. All systems were characterised by FT-IR, differential scanning calorimetry, X-ray diffraction, flowability and dissolution techniques. Mini-tablets were prepared using the system with the optimum dissolution profile and flowability. Tensile strengths, content uniformity and dissolution profiles of the mini-tablets were evaluated. The effects of different excipients and storage conditions on mini-tablet properties were also studied. The optimised rapid-release LOR mini-tablets were further evaluated for their in vivo pharmacokinetic profile. The co-evaporate of LOR with PLU showed significantly faster dissolution and superior flowability and was evaluated together with three directly compressible excipients (Cellactose® 80, StarLac® (STA) and Emcompress®) for mini-tablet formulation. The formulation with STA provided the optimum results in terms of tensile strength content uniformity and rapid drug release following a 3-month stability study and was selected for further in vivo evaluation. The pharmacokinetic profile indicated the potential of the mini-tablets achieving rapid release and increased absorption of LO

Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery

Purpose The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ( L -arginine and L -leucine) (0.5–1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, L -leucine was significantly superior in enhancing the aerosolization performance ( L- arginine:%FPF 27.61 ± 4.49–26.57 ± 1.85; FPD 12.40 ± 0.99–19.54 ± 0.16 μg and MMAD 2.18 ± 0.35–2.98 ± 0.25 μm, L -leucine:%FPF 36.90 ± 3.6–43.38 ± 5.6; FPD 18.66 ± 2.90–21.58 ± 2.46 μg and MMAD 2.55 ± 0.03–3.68 ± 0.12 μm). Incorporating L -leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi’s pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L -leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment. Conclusion The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery

Stereoselective synthesis and X-ray structure determination of novel 1,2-dihydroquinolinehydrazonopropanoate derivatives

A novel series of 1,2-dihydroquinolinhydrazonopropanoate have been synthesized via a convenient aza-Michael addition reaction between hydrazinylquinolinones and ethyl propiolate in ethanol under refluxing temperature. The structures for all obtained products were confirmed with FTIR, NMR spectrums, as well as mass spectrometry. In addition, the monoclinic structure for compounds 8a, 8c, and 8d was also confirmed via X-ray crystallography analyses. The E-configuration for the obtained products was confirmed form the X-ray analysis. On the other hand, the crystal packing shows that the intermolecular and hydrogen bonds between atoms are parallel to the bc plan

Harmonic rejection using multi-synchronous reference frame technique for CSI-based distributed generation with grid voltage distortion

In the midst of the growing penetration of renewable energy resources and Distributed Generation (DG), power quality is one of the main concerns. Achieving low total harmonic distortion (THD) of exported current using low switching frequency inverters is a challenge, especially under conditions of severe utility voltage distortion. Previous work depended on the wide bandwidth of passive filters accompanying high switching frequency inverters, which enables controlling fast tracking of pure sinusoid reference current. This paper presents a control structure for current source inverter-based distributed generation based on Multi-Synchronous Reference Frame, to reject the effect of utility distortion and attain high quality output current. This solution is applicable for low switching frequency inverters, with limited passive filter bandwidth. Experimental results validate the proposed technique.Scopu

Risk factors for the development of flank hernias and bulges following surgical flank approaches to the kidney in adults

Objectives: To evaluate the incidence and risk factors for the development of flank incisional hernias or bulges following surgical flank approaches to the kidney. Patients and methods: In all, 100 consecutive adult patients who underwent variable renal surgeries via flank approaches were included in this prospective study. The incidence and risk factors for flank hernias and bulges were studied at 1- and 6-months postoperatively. Results: At 6 months postoperatively, the incidence of flank bulge was 14% and for lumbar hernia was 10%. The univariate analysis showed 13 significant factors to be associated with the occurrence of a flank bulge or hernia following flank incisions. When the significant risk factors in the univariate analysis were studied by multivariate analysis, using a logistic regression analysis, four independent risk factors were identified. These were: body mass index (BMI) ≥26.3 kg/m2 (P = 0.04), the use of a self-retaining retractor during surgery (P = 0.02), not preserving or identifying the neurovascular bundle (NVB) during surgery (P = 0.028), and postoperative abdominal distention (P = 0.001). Moreover, all cases included in our study who underwent en masse wound closure, developed surgical wound infection or who had constipation developed postoperative flank bulge or hernia. Conclusion: High BMI, the use of self-retaining retractor, not identifying or preserving the NVB, postoperative abdominal distention, en masse wound closure, surgical wound infection, and constipation are significant risk factors associated with postoperative flank hernia and bulge. Keywords: Abdominal hernia, Flank, Hernia, Incisional hernia, Postoperative herni