ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

A Design Task for Sivas Grand Mosque’s Minaret: Vertical Construction/Formal Articulation/Visual Stimuli

As well as a design process, experimental practices in architectural education are associated with the analytical approaches of visual thinking and visual reasoning. The main purpose of this study was to explore creative methods for devising a vertical construction through visual reasoning. In terms of experimental practices, design research is based on exploration while the primary research area in architecture is reframed by constantly renewed approaches. Accordingly, the hypothesis of this study was that creative methods would improve when the creation of a vertical construction in architectural education is nourished by visual stimuli. The study searched for a construction that plasticized the vertical spatiality of Sivas Grand Mosque’s minaret. The method was shaped by a prerequisite dialogue that rests on visual stimuli. The expected outcome of this dialogue was that the minaret as a pure form would be subjected to an abstraction and, a design proposal then developed for its current structural problems. The results indicated a two-fold appreciation of design. First, when the minaret was maintained within the idea of stabilization rather than being construed as a pure form, the search for a creative method of vertical construction was handled in the context of static preservation. Second, when Sivas Grand Mosque’s minaret as an imaginary design tool was construed as a pure form and the abstraction level increased through visual reasoning, the outcomes gradually demonstrated an approach akin to experimental practices

Effect of fungicidal agents on the initial growth of spring wheat plants

This study provides a comparative assessment of the effectiveness of active ingredients of fungicidal preparations and in a mixture with organomineral fertilizers on reducing the infection of seed and the germination of spring wheat plants in the initial phases of ontogenesis. For the research, on 8 different combinations of active ingredients fungicides in pure form and in a mixture with organomineral fertilizer. The application of fungicide did not affect the seed growth energy, but in most cases the germination rate increased by 4%. Seed dressing had a retardant effect on germination of the plant’s organs, and the fertiliser stimulating effect was shown in Variant 1 (Protioconazole + Tebuconazole + fertiliser). The efficiency of disinfectants against seed diseases reached 96% against general contamination and 56-93% against pathogenic microflora, and in a mixture with organomineral fertilizer, the efficiency is reduced by 13%. High and stable efficiency was manifested in drugs based on the active substances Tebuconazole + Flutriafol (80 + 80 g/l). Protioconazole + Tebuconazole (250+150 g/l) with net efficiency of 83-93%. As a result of the research, the effect of pickling with fungicides was determined on the basis of various combinations of active substances in pure form and with the addition of organomineral fertilizer as a growth stimulator.

Light scattering detector based on light-emitting diodes-Solar cells for a flow analysis of Warfarin in pure form and pharmaceutical formulations

Continuous turbidimetric analysis (CTA) for a distinctive analytical application by employing a homemade analyser (NAG Dual & Solo 0-180°) which contained two consecutive detection zones (measuring cells 1 & 2) is described. The analyser works based on light-emitting diodes as a light source and a set of solar cells as a light detector for turbidity measurements without needing further fibres or lenses. Formation of a turbid precipitated product with yellow colour due to the reaction between the warfarin and the precipitation reagent (Potassium dichromate) is what the developed method is based on. The CTA method was applied to determine the warfarin in pure form and pharmaceutical formulations in the concentration range from 2.0-16& 0.7-16 mmol/L with 0.58 and 0.55 mmol/L of the limit of detections. The correlation coefficients (r) of the developed method were 0.9977 and 0.9981 for cell 1 and 2 respectively. For validation of proposed method, the ICH guidelines were followed. The developed method was successfully applied for the determination of Warfarin in pure and pharmaceutical preparations. In addition, the method can be considered as a quality control method and conveniently used for routine analysis in laboratories since the method permits quantitatively determination of 60 samples/h.

Micellar-Enhanced Spectrofluorimetric Method for Quantification of Diclofenac Potassium in Pure Form, in Pharmaceutical Preparations and Human Plasma

A rapid, simple and economical spectrofluorimetric method for the determination of diclofenac potassium in pure form, in pharmaceutical preparations and in human plasma has been developed. The method is based on the enhancement of the fluorescence signal of diclofenac potassium by the addition of sodium dodecyl sulphate in McIvaine buffer with a pH of 5. Different experimental conditions such as buffer type, pH, type and concentration of surfactants were investigated. The fluorescence intensity of the solution was recorded at 361 nm after excitation at 243 nm. The method shows linearity in the concentration range of 0.2 μg mL–1–10 μg mL–1 with a good correlation coefficient of 0.997. The relative standard deviation value was 3.62 (n = 7). The limit of detection and limit of quantification were calculated to be 2.84 × 10–3 μg mL–1 and 9.47 × 10–3 μg mL-1, respectively. The effect of excipients and co-administrated drugs was investigated and no interference was observed. The method was successfully applied for the determination of diclofenac potassium in pure form, in pharmaceutical products and in human plasma. The percentage recoveries obtained ranged from 100.25% to 102.16% for pure form and 97.50% to 102.00% for pharmaceutical products and from 98.50% to 101.67% for human plasma.

Validated Capillary Zone Electrophoretic Determination of Avanafil and Dapoxetine Hydrochloride in their Pure form and Pharmaceutical Preparation

Aims: In this study, a simple, green, and rapid capillary zone electrophoresis (CZE) method coupled with a diode array detector (DAD) was applied for the analysis of avanafil (AVA) and dapoxetine hydrochloride (DAP) as a binary mixture using vardenafil (VAR) as an internal standard (IS) in pure form and pharmaceutical formulation. Methodology: The separation was done using fused silica capillary (58.5 cm total length, 50 cm effective length, and 50 μm internal diameter) and the running background electrolyte (BGE) was 100 mM acetate buffer at pH 3.6. During the separation process, the applied voltage was 30 KV, while the temperature was 25 °C. The sample injection was applied at a pressure of 50 mbar for 10 s, and detection was carried out at 210 nm for DAP and 248 nm for AVA and VAR. Results: Analysis of the tested drugs and the internal standard was carried out in less than 6.5 min, where the migration times were 4.29, 4.90, and 6.02 min for IS, DAP and AVA respectively. The proposed method showed linearity in the concentration range 5-80 and 5-70 μg/mL with correlation coefficients 0.9996 and 0.9999 for AVA and DAP respectively. The limit of detection (LOD) was 0.523 and 0.531 for AVA and DAP respectively, while the limit of quantification (LOQ) was 1.585 and 1.608 in respective order. The Peak purity and identity in the proposed method were validated by DAD. Conclusion: The proposed CZE method was validated according to ICH guidelines and applied successfully for the estimation of AVA and DAP in their combined pharmaceutical preparation.

TAXIS REPRESENTANTS IN THE GERMAN AND DUTCH LANGUAGES

Постановка задачи. В статье описываются таксисные репрезентанты в немецком и нидерландском языках, каковыми являются полипропозитивные высказывания с предложными девербативами с таксисными предлогами темпоральной и обстоятельственной семантики. Результаты. Описаны высказывания двух типов (примарного и секундарного), являющиеся ядерными и периферийными конституентами функционально-семантического субполя зависимого таксиса в немецком и нидерландском языках. К ядерным конституентам относятся высказывания примарного типа с таксисными предлогами темпоральной семантики, а к периферийным конституентам следует относить высказывания секундарного типа с таксисными предлогами обстоятельственной семантики. Таксисные предлоги темпоральной семантики маркируют примарно-таксисную семантику одновременности и разновременности, а таксисные предлоги обстоятельственной семантики эксплицируют секундарно-таксисную семантику одновременности. Выводы. Обследованные высказывания примарного и секундарного типов являются прототипическими репрезентантами как примарно-таксисных значений одновременности и разновременности в «чистом виде», так и секундарно-таксисных значений одновременности, совмещенных с сопутствующими обстоятельственными значениями (условия, уступки, цели, образа действия и др.). Problem statement. The article describes taxis representatives in German and Dutch, which are polypropositive statements with prepositional deverbatives with taxis prepositions of temporal and circumstantial semantics. Results. The statements of two types (primary and secondary) are described, which are the core and peripheral constituents of the functional-semantic subfield of the dependent taxis in the German and Dutch languages. The core constituents include statements of the primary type with taxis prepositions of temporal semantics, while the peripheral constituents should include statements of the secondary type with taxis prepositions of circumstantial semantics. Taxis prepositions of temporal semantics mark the primary taxis semantics of simultaneity and non-simultaneity, and taxis prepositions of circumstantial semantics explicate the secondary taxis semantics of simultaneity. Conclusion. The examined statements of the primary type and of the secondary type are prototypical representatives of both primary-taxis values of simultaneity and non-simultaneity in «pure form», and secondary taxis values of simultaneity, combined with concomitant circumstantial values (conditions, concessions, purpose, mode of action, etc.).