Brighteness-dependent visual attractiveness of the human body for horse flies (Diptera: Tabanidae): a field experiment.

The landing patterns of blood-sucking females (Diptera: Tabanidae) are largely influenced by their visual perceptions. When attacking humans, the shape of different body parts and overall brightness of the body could be the factors determining the place of blood-sucking. The visual attractiveness of the human body for tabanids was investigated through a black and a white mannequin in the Danube floodplain, Slovakia.

Insider trading.

This paper describes a dataset capturing insider trading activity at publicly traded companies. Investors and investment analysts demand this information because executives, directors and large shareholders are expected to have more intimate knowledge of their company's prospects than outsiders. Insider stock sales and purchases may reveal information about the firm's business not disclosed in financial statements.

Frequency and waveform dependence of alternating current electrospinning and their uses for drug dissolution enhancement.

The effect of different frequencies and waveforms was investigated for the first time on alternating current electrospinning (ACES). PVPVA64, a polyvinylpyrrolidone-vinyl acetate copolymer was selected for the experiments as an important matrix for amorphous solid dispersions but never processed with ACES. It has been proved that ACES could be operated in a wide range of frequencies (40-250 Hz) and using different waveforms (sinusoidal, square, triangle, saw tooth) without significant changes in fiber morphology.

End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration.

An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a mixed suspension mixed product removal crystallizer. The crystallizer was directly connected to a continuous filtration carousel device, thus the crystallization, filtration and drying of acetylsalicylic acid (ASA) was carried out in an integrated 2-step process.

Electrospun amorphous solid dispersions of meloxicam: Influence of polymer type and downstream processing to orodispersible dosage forms.

The objectives of this work were to develop meloxicam based amorphous solid dispersion through electrospinning technique and evaluate the effect of the polymeric matrix on the physicochemical properties of the fibers and the downstream processing ability to orodispersible dosage forms. Drug - polymer interactions formed between Eudragit E and meloxicam, confirmed through Raman and 1HNMR spectra, enabled the development of fibers from ethanol, thus allowing an increased production rate compared to PVPk30 where a DMF:THF solvent system was suitable. Microflux dissolution-permeation studies showed a significantly higher diffusion from amorphous solid dispersions compared to crystalline meloxicam.

Data fusion strategies for performance improvement of a Process Analytical Technology platform consisting of four instruments: An electrospinning case study.

The aim of this work was to develop a PAT platform consisting of four complementary instruments for the characterization of electrospun amorphous solid dispersions with meloxicam. The investigated methods, namely NIR spectroscopy, Raman spectroscopy, Colorimetry and Image analysis were tested and compared considering the ability to quantify the active pharmaceutical ingredient and to detect production errors reflected in inhomogeneous deposition of fibers. Based on individual performance the calculated RMSEP values ranged between 0.

Corona alternating current electrospinning: A combined approach for increasing the productivity of electrospinning.

Corona alternating current electrospinning (C-ACES), a scaled-up productivity electrospinning method was developed by combining the intense forces of the alternating electrostatic field and a sharp-edged spinneret design with increased free surface. C-ACES reached two orders of magnitude higher productivity (up to 1200 mL/h) than the classical single needle direct current electrospinning (DCES) without any alteration of fiber properties. Polyvinylpyrrolidone K90 (PVPK90), a water soluble high molecular weight nonionic polymer was processed for the first time with single needle alternating current electrospinning (ACES) and C-ACES in order to prepare fast dissolving amorphous solid dispersions of spironolactone (SPIR), a poorly water-soluble antihypertensive model drug.

Continuous manufacturing of orally dissolving webs containing a poorly soluble drug via electrospinning.

An orally dissolving web (ODW) formulation of poorly soluble carvedilol (CAR) was developed and manufactured continuously using electrospinning (ES) as a key technology. Phase solubility tests revealed that hydroxypropyl-β-cyclodextrin (HPβCD) solubilizer alone cannot ensure sufficient solubility (6.25 mg CAR in 20 mL) in the oral cavity even if citric acid was present to ionize the basic drug.

The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations-printability-process modulation, with consecutive effects on in vitro release, stability and degradation.

The three dimensional printing (3DP) in the pharmaceutical domain constitutes an alternative, innovative approach compared to the conventional production methods. Fused deposition modelling (FDM), is a simple, cost-effective 3DP technique, however the range of pharmaceutical excipients that can be applied for this methodology is restricted. The study set to define the requirements of the FDM printability, using as technical support custom made, pharmaceutical polymer based filaments and to evaluate if these new dosage forms can live up to the current GMP/GCP quality standards.

Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation.

Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone--vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer. Scanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES samples.

The role of the insula in the parieto-frontomedial epileptic network. Clues from successful surgical treatment.

We present a case of MRI negative SMA seizure with the seizure onset zone in the secondary leg area on the superior bank of the Sylvian fissure, localized with multiscale electro-clinical and neuroradiological examinations. The 34-year-old female patient's intractable epilepsy started at age 14. She had diffuse pain aura in her left leg followed by tonic posturing with fully preserved consciousness suggesting parieto-fronto-medial seizure propagation.

The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations.

In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%.

Oral bioavailability enhancement of flubendazole by developing nanofibrous solid dosage forms.

The bioavailability of the anthelminthic flubendazole was remarkably enhanced in comparison with the pure crystalline drug by developing completely amorphous electrospun nanofibres with a matrix consisting of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone. The thus produced formulations can potentially be active against macrofilariae parasites causing tropical diseases, for example, river blindness and elephantiasis, which affect altogether more than a hundred million people worldwide. The bioavailability enhancement was based on the considerably improved dissolution.

Novel Alternating Current Electrospinning of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) Nanofibers for Dissolution Enhancement: The Importance of Solution Conductivity.

Novel, high-yield alternating current electrospinning (ACES) and direct current electrospinning methods were investigated to prepare high-quality hydroxypropylmethylcellulose acetate succinate (HPMCAS) fibers for the dissolution enhancement of poorly soluble spironolactone. Although HPMCAS is of great pharmaceutical importance as a carrier of marketed solid dispersion-based products, it was found to be unprocessable using electrospinning. Addition of small amounts of polyethylene oxide as aid polymer provided smooth fibers with direct current electrospinning but strongly beaded products with ACES.

Investigation and Mathematical Description of the Real Driving Force of Passive Transport of Drug Molecules from Supersaturated Solutions.

The aim of this study was to investigate the impact of formulation excipients and solubilizing additives on dissolution, supersaturation, and membrane transport of an active pharmaceutical ingredient (API). When a poorly water-soluble API is formulated to enhance its dissolution, additives, such as surfactants, polymers, and cyclodextrins, have an effect not only on dissolution profile but also on the measured physicochemical properties (solubility, pK, permeability) of the drug while the excipient is present, therefore also affecting the driving force of membrane transport. Meloxicam, a nonsteroidal anti-inflammatory drug, was chosen as a poorly water-soluble model drug and formulated in order to enhance its dissolution using solvent-based electrospinning.

Specific detection and quantitation of bovine IgG in bioreactor derived mouse mAb preparations.

Monoclonal antibody and recombinant protein production benefits greatly from bovine serum as an additive. The caveat is that bovine serum IgG, co-purifies with mAbs and IgG Fc-containing fusion proteins and it presents a contaminant in the end products. In order to analytically validate the products, species specific reagents are needed that react with bovine IgG exclusively.

Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion.

Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation is in a quite early phase. Development of high speed electrospinning opened up the possibility to study tableting of electrospun solid dispersions (containing polyvinylpyrrolidone-vinyl acetate and itraconazole [ITR] in this case). This work was conducted to investigate the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting.

Quantification and handling of nonlinearity in Raman micro-spectrometry of pharmaceuticals.

This work demonstrates how nonlinearity in Raman spectrometry of pharmaceuticals can be handled and accurate quantification can be achieved by applying certain chemometric methods including variable selection. Such approach proved to be successful even if the component spectra are very similar or spectral intensities of the constituents are strongly different. The relevant examples are: blends of two crystalline forms of carvedilol ("CRYST-PM" blend) and a three-component pharmaceutical model system ("PHARM-TM" blend).

AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution.

Alternating current electrospinning (ACES) capable to reach multiple times higher specific productivities than widely used direct current electrospinning (DCES) was investigated and compared with DCES to prepare drug-loaded formulations based on one of the most widespread polymeric matrix used for commercialized pharmaceutical solid dispersions, hydroxypropylmethylcellulose 2910 (HPMC). In order to improve the insufficient spinnability of HPMC (both with ACES and DCES) polyethylene oxide (PEO) as secondary polymer with intense ACES activity was introduced into the electrospinning solution. Different grades of this polymer used at as low concentrations in the fibers as 0.

[THE PROPAGATION AND SEMIOLOGY OF FOCAL EPILEPTIC SEIZURES. CASES CONNECTED TO THE INSULA. THEORETICAL CONSIDERATIONS].

Study Objectives: The developing of diagnostical examinations in epileptology provides new challenges in seizure semiology. On the analysis of seizures it is important to examine the mechanisms of their propagation. The brain connectivity (based on the neuroimaging), the shadowing of the movement of excessive neuronal activity (based on computerized EEG and MEG methods), the cognition of the physiological and pathological brain networks are the footstone of the epileptic seizure propagation.

Alternating current electrospinning for preparation of fibrous drug delivery systems.

Alternating current electrospinning (ACES) was compared to direct current electrospinning (DCES) for the preparation of drug-loaded nanofibrous mats. It is generally considered that DCES is the solely technique to produce nanofibers using the electrostatic force from polymer solutions, however, less studied and also capable ACES provides further advantages such as increased specific productivities. A poorly water-soluble drug (carvedilol) was incorporated into the fibers based on three different polymeric matrices (an acid-soluble terpolymer (Eudragit(®) E), a base-soluble copolymer (Eudragit(®) L 100-55) and a nonionic homopolymer (polyvinylpyrrolidone K90)) to improve the dissolution of the weak base drug under different pH conditions.

In vitro dissolution-permeation evaluation of an electrospun cyclodextrin-based formulation of aripiprazole using μFlux™.

Since it is a well-known fact that among the newly discovered active pharmaceutical ingredients the number of poorly water soluble candidates is continually increasing, dissolution enhancement of poorly water soluble drugs has become one of the central challenges of pharmaceutical studies. So far the preclinical studies have been mainly focused on formulation methods to enhance the dissolution of active compounds, in many cases disregarding the fact that the formulation matrix not only affects dissolution but also has an effect on the transport through biological membranes, changing permeation of the drug molecules. The aim of this study was to test an electrospun cyclodextrin-based formulation of aripiprazole with the novel μFlux apparatus, which monitors permeation together with dissolution, and by this means better in vitro-in vivo correlation is achieved.

[Treatment of osteoporotic vertebral compression fractures with PMMA-augmented pedicle screw fixation].

Background: Over the last few decades many innovative operation technique were developed due to the increase of porotic vertebral fractures. These new techniques aim to reach the required stability of the vertebral column. In case of significant instability, spinal canal stenosis or neural compression, decompressive intervention may be necessary, which results in further weakening of the column of the spine, the minimal invasive percutan vertebroplasty is not an adequate method to reach the required stability, that is why insertion of complementary pedicular screws is needed.