Developing and scaling up captopril-loaded electrospun ethyl cellulose fibers for sustained-release floating drug delivery

In this work ethyl cellulose (EC) was used as a matrix polymer and loaded with captopril, with the goal to fabricate electrospun fibers as potential sustained-release floating gastro-retentive drug delivery systems. Fibers were prepared with monoaxial and coaxial electrospinning, and both bench-top and scaled-up (needle-based) methods were explored. With monoaxial electrospinning, EC-based fibers in the shape of cylinders and with smooth surfaces were obtained both at 1 and 20 mL/h. For coaxial electrospinning, the drug was encapsulated in the core and fibers generated with core/shell feeding rates of 0.5/1 and 5/10 mL/h. These fibers were cylindrical in shape with a wrinkled surface, and confocal microscopy suggested them to have a core/shell structure. X-ray diffraction and differential scanning calorimetry results showed that all the fibers were amorphous. The encapsulation efficiency of all the formulations was almost 100%. Release studies in simulated gastric fluid indicated that the monoaxial electrospun fibers gave slower release profiles compared with a physical mixture of captopril and EC, but there was still an initial “burst” of release at the start of the experiment. Fibers with low drug-loading (9.09% w/w) showed a slower release than fibers with high loading (23.08% w/w). The coaxial fibers exhibited sustained release profiles with reduced initial burst release. Both monoaxial and coaxial fibers could float on the surface of simulated gastric fluid for over 24 h at 37 °C. After storage under ambient conditions (19–21 °C, relative humidity 30–40%) for 8 weeks, all the fibers remained amorphous and the release profiles had no significant changes compared with fresh fibers. This work thus highlights the potential of coaxial electrospinning for fabricating a sustained-release floating gastro-retentive drug delivery system for captopril

An improved history-match for layer spreading within the Sleipner plume including thermal propagation effects

The Sleipner CO2 storage operation has been injecting CO2 since 1996, and the growth of the plume has been intensively monitored using time-lapse seismic techniques. Detailed history-matching of the topmost CO2 layer has proven challenging. This paper summarizes results from a series of flow simulations examining two key parameters affecting CO2 mobility: permeability heterogeneity and fluid temperatures within the plume. The best match to the observed distribution of CO2 was achieved by including high permeability channels in the reservoir flow model, as observed on seismic data. Thermal models suggests that CO2 enters the top sand layer 7 °C warmer than the ambient reservoir. The resulting reduction in the density and viscosity of CO2 does not significantly improve the fit between seismic and simulation

Biocompatible hydroxy double salt tablet formulations

Generally, commercial extended release tablets are core-based, which can cause problems for certain patients if they split them prior to ingestion. There is a need to develop non-core-based extended release tablets. We have previously reported the synthesis of two new biocompatible hydroxy double salts (HDSs), [Mg2Zn3(OH)8]Cl2⋅3.4H2O (MgZn–Cl) and [Fe2.4Zn2.6(OH)8]Cl2⋅2H2O (FeZn–Cl) (J. Mater. Chem. B 2016, 4, 5789), and found them to be good candidates for the extended release of diclofenac (Dic), ibuprofen (SI) and valproate (Val) (Appl. Clay. Sci. 2022, 221, 106456). Here we build on these previous results and report scale-up synthesis of MgZn–Cl and FeZn–Cl loaded with Dic, SI, and Val. The scaled-up products were blended with excipients and formulated into non-core based tablets. The post-compression parameters of the HDS-based tablets were assessed against the pharmacopeia requirements (friability, weight, and dose uniformity) and all passed the tests. Drug release studies were carried out using the paddle method (USPII) in conditions representative of the gastrointestinal tract. The HDS tablets were found to meet the pharmacopeia requirements for modified release dosage forms and showed similar release profiles to current commercial formulations. It is thus possible to develop modified release non-core based tablets using HDSs. These have additional benefits over standard commercial tablets, because the presence of the essential elements Zn, Fe and/or Mg in the layers can compensate for deficiencies induced over long-term treatment, and enhance therapeutic efficacy in some cases. Furthermore, the buffering effect of the HDS layers has the potential to prevent the gastric irritation often associated with the use of non-steroidal anti-inflammatory drugs

Anti-emetic effects of thalidomide: evidence, mechanism of action, and future directions

The rationale for using thalidomide (THD) as a treatment for nausea and vomiting during pregnancy in the late 1950s appears to have been based on its sedative or hypnotic properties. In contrast to contemporaneous studies on the anti-emetic activity of phenothiazines, we were unable to identify publications reporting preclinical or clinical evaluation of THD as an anti-emetic. Our survey of the literature revealed a clinical study in 1965 showing THD reduced vomiting in cancer chemotherapy which was substantiated by similar studies from 2000, particularly showing efficacy in the delayed phase of chemotherapy-induced nausea and vomiting. To identify the mechanism(s) potentially involved in thalidomide's anti-emetic activity we reviewed its pharmacology in the light of nausea and vomiting mechanisms and their pharmacology with a particular emphasis on chemotherapy and pregnancy. The process identified the following potential mechanisms: reduced secretion of Growth Differentiation Factor 15, suppression of inflammation/prostaglandin production, downregulation of cytotoxic drug induced upregulation of iNOS, and modulation of BK (KCa1.1) channels and GABAA/glutamate transmission at critical points in the emetic pathways (nucleus tractus solitarius, area postrema). We propose ways to investigate these hypothesized mechanisms and discuss the associated challenges (e.g., objective quantification of nausea) in addition to some of the more general aspects of developing novel drugs to treat nausea and vomiting

Aspects of service-dominant logic and its implications for tourism management: examples from the hotel industry.

Author's draft of article submitted to Tourism Management, also available on Surrey University e-prints repository. The definitive version was subsequently published by Elsevier and is available online at http://www.sciencedirect.com/This paper introduces the concept of service-dominant logic as a research paradigm in marketing management. It does so in the context of tourism management‟s need to engage with wider debates within the mainstream management literature. Moreover it demonstrates the importance of service-dominant logic in uncovering the role played by co-production and co-creation in the tourism industry. These ideas are developed in detail through a case study of the UK hotel industry that draws on new empirical research undertaken by the authors.Funding provided by ESRC and the Advanced Institute of Managemen

Stable Dried Catalase Particles Prepared by Electrospraying

Therapeutic proteins and peptides are clinically important, offering potency while reducing the potential for off-target effects. Research interest in developing therapeutic polypeptides has grown significantly during the last four decades. However, despite the growing research effort, maintaining the stability of polypeptides throughout their life cycle remains a challenge. Electrohydrodynamic (EHD) techniques have been widely explored for encapsulation and delivery of many biopharmaceuticals. In this work, we explored monoaxial electrospraying for encapsulation of bovine liver catalase, investigating the effects of the different components of the electrospraying solution on the integrity and bioactivity of the enzyme. The catalase was successfully encapsulated within polymeric particles made of polyvinylpyrrolidone (PVP), dextran, and polysucrose. The polysorbate 20 content within the electrospraying solution (50 mM citrate buffer, pH 5.4) affected the catalase loading-increasing the polysorbate 20 concentration to 500 μg/mL resulted in full protein encapsulation but did not prevent loss in activity. The addition of ethanol (20% v/v) to a fully aqueous solution improves the electrospraying process by reducing surface tension, without loss of catalase activity. The polymer type was shown to have the greatest impact on preserving catalase activity within the electrosprayed particles. When PVP was the carrier there was no loss in activity compared with fresh aqueous solutions of catalase. The optimum particles were obtained from a 20% w/v PVP or 30% w/v PVP-trehalose (1:1 w/w) solution. The addition of trehalose confers stability advantages to the catalase particles. When trehalose-PVP particles were stored at 5 °C, enzymatic activity was maintained over 3 months, whereas for the PVP-only analogue a 50% reduction in activity was seen. This demonstrates that processing catalase by monoaxial electrospraying can, under optimised conditions, result in stable polymeric particles with no loss of activity

Dual-Mode and Label-Free Detection of Exosomes from Plasma Using an Electrochemical Quartz Crystal Microbalance with Dissipation Monitoring

The biomolecular contents of extracellular vesicles, such as exosomes, have been shown to be crucial in intercellular communication and disease propagation. As a result, there has been a recent surge in the exploration of novel biosensing platforms that can sensitively and specifically detect exosomal content such as proteins and nucleic acids, with a view toward application in diagnostic assays. Here, we demonstrate dual-mode and label-free detection of plasma exosomes using an electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). The platform adopts a direct immunosensing approach to effectively capture exosomes via their surface protein expression of CD63. By combining QCM-D with a tandem in situ electrochemical impedance spectroscopy measurement, we are able to demonstrate relationships between mass, viscoelasticity and impedance inducing properties of each functional layer and analyte. In addition to lowering the limit of detection (by a factor of 2-4) to 6.71 × 107 exosome-sized particles (ESP) per mL in 25% v/v serum, the synergy between dissipation and impedance response introduces improved sensing specificity by offering further distinction between soft and rigid analytes, thereby promoting EQCM-D as an important technique for exosome analysis

Simultaneous differential scanning calorimetry – synchrotron X-ray powder diffraction : a powerful technique for physical form characterisation in pharmaceutical materials

© 2016 American Chemical Society. We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC

Search for B0s oscillations using inclusive lepton events

A search for B0s oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to B0s mixing is obtained by identifying subsamples of events having a B0s purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Deltam_s>9.5ps^-1 at 95% CL. Combining with the ALEPH D-s based analyses yields Deltam_s>9.6ps^-1 at 95% CL.Comment: 23 pages, 10 figure