Quality risk assessment and DoE – Practiced validated stability-indicating chromatographic method for quantification of Rivaroxaban in bulk and tablet dosage form

A systematic DoE and Analytical Quality by Design (AQbD) approach was utilized for the development and validation of a novel stability indicating high-performance thin–layer chromatographic (HPTLC) method for Rivaroxaban (RBN) estimation in bulk and marketed formulation. A D-optimal design was used to screen the effect of solvents, volume of solvents, time from spotting to development and time for development to scanning. ANOVA results and Pareto chart revealed that toluene, methanol, water and saturation time had an impact on retention time. The critical method and material attributes were further screened by Box-Behnken design (BBD) to achieve optimal chromatographic condition. A stress degradation study was carried out and structure of major alkaline degradant was elaborated. According to the design space, a control strategy was used with toluene: methanol: water (6:2:2) and the saturation time was 15 min. A retention factor (RF) of 0.59 ± 0.05 was achieved for RBN using chromatographic plate precoated with silica gel at detection wavelength 282 nm with optimized conditions. The linear calibration curve was achieved in the concentration range of 200–1,200 ng/band with r 2 > 0.998 suggesting good coordination between analyte concentration and peak areas. The quadratic model was demonstrated as the best fit model and no interaction was noted between CMAs. The optimized HPTLC method was validated critically as stated in International Conference on Harmonization (ICH) Q2 (R1) guideline and implemented successfully for stress degradation study of RBN. The developed HPTLC method obtained through AQbD application was potentially able to resolve all degradants of RBN achieved through forced degradation study. The obtained results demonstrate that a scientific AQbD approach implementation in HPTLC method development and stress degradation study drastically minimizes the number of trials in experiments, ultimately time and cost of analysis could be minimized.

Adapting and validating the log quadratic model to derive under-five age- and cause-specific mortality (U5ACSM): a preliminary analysis

Background The mortality pattern from birth to age five is known to vary by underlying cause of mortality, which has been documented in multiple instances. Many countries without high functioning vital registration systems could benefit from estimates of age- and cause-specific mortality to inform health programming, however, to date the causes of under-five death have only been described for broad age categories such as for neonates (0–27 days), infants (0–11 months), and children age 12–59 months. Methods We adapt the log quadratic model to mortality patterns for children under five to all-cause child mortality and then to age- and cause-specific mortality (U5ACSM). We apply these methods to empirical sample registration system mortality data in China from 1996 to 2015. Based on these empirical data, we simulate probabilities of mortality in the case when the true relationships between age and mortality by cause are known. Results We estimate U5ACSM within 0.1–0.7 deaths per 1000 livebirths in hold out strata for life tables constructed from the China sample registration system, representing considerable improvement compared to an error of 1.2 per 1000 livebirths using a standard approach. This improved prediction error for U5ACSM is consistently demonstrated for all-cause as well as pneumonia- and injury-specific mortality. We also consistently identified cause-specific mortality patterns in simulated mortality scenarios. Conclusion The log quadratic model is a significant improvement over the standard approach for deriving U5ACSM based on both simulation and empirical results.

Facile Fabrication of Amino-Functionalized MIL-68(Al) Metal-organic Framework for Effective Adsorption of Arsenate (As(V))

An amino-functionalized MIL-68(Al) metal-organic framework (amino-MIL-68(Al) MOF) was synthesized by solvothermal method and then characterized by FESEM, XRD, FTIR, EDX-mapping, and BET-BJH techniques. In order to predict arsenate (As(V)) removal, a robust quadratic model (R2 > 0.99, F-value = 2389.17 and p-value < 0.0001) was developed by the central composite design (CCD) method and then the genetic algorithm (GA) was utilized to optimize the system response and four independent variables. The results showed that As(V) adsorption on MOF was affected by solution pH, adsorbent dose, As(V) concentration and reaction time, respectively. Predicted and experimental As(V) removal efficiencies under optimal conditions were 99.45 and 99.87 %, respectively. The fitting of experimental data showed that As(V) adsorption on MOF is well described by the nonlinear form of the Langmuir isotherm and pseudo-second-order kinetic. At optimum pH 3, the maximum As(V) adsorption capacity was 74.29 mg/g. Thermodynamic studies in the temperature range of 25 to 50 °C showed that As(V) adsorption is a spontaneous endothermic process. The reusability of MOF in ten adsorption/regeneration cycles was studied and the results showed high reusability of this adsorbent. The highest interventional effect in inhibiting As(V) adsorption was related to phosphate anion. The results of this study showed that amino-MIL-68(Al) can be used as an effective MOF with a high surface area (> 1000 m2/g) and high reusability for As(V)-contaminated water.

Statistical models expressing relations between soil moisture, aggregate speed, and tillage depth at plowing and cultivation

The study is based on a one-year field experiment (2019) in the land of the Chirpan region located in central Bulgaria. The agrotechnical operations of plowing and cultivation, applied in technology for the production of sunflower, are studied. Four models (Linear, Exponential, Logarithmic, and Quadratic) were compared at p < 0.05, defining the relation between soil moisture, aggregate speed, and the uniformity of the soil index Tillage depth during plowing and cultivation. It was found that in plowing at a speed of 4 km/h the Quadratic model described the relation between soil moisture and tillage depth with the highest coefficient of determination (R2 = 0.682). Relating to plowing at a speed of 4.5 km/h the most suitable is the Exponential model (R2 = 0.729), i.e. about 68.2% and 72.9% of the variations in tillage depth are due to the influence of the moisture of the soil. The coefficients of determination, calculated when cultivating at speeds of 8 km/h (R2 = 0.526) and 9 km/h (R2 = 0.557), show that the Quadratic model most strongly (52.6% and 55.7%) determines the relation between soil moisture and tillage depth. The developed models could be used to optimize the control systems of agricultural machinery.

Anisotropic stellar model of neutron stars in f(T) gravity with off-diagonal tetrad

In this paper, we develop a new class of analytical solutions describing anisotropic stellar structures of observed neutron stars using modified f(T) gravity. We use the off-diagonal tetrad that is best suitable for studying spherically symmetric objects in f(T) gravity. We develop exact solutions in the quadratic model of f(T) gravity by introducing physically reliable metric potentials that can describe a wide range of astrophysical systems. We then apply the model to investigate the stellar structures of four observed compact stars, 4U 1538-52, J0437-4715, J0030+0451, and 4U 1820-30. We calculate the values of model parameters for the stellar objects under examination in this paper. Comprehensive graphical analysis shows that the model describing anisotropic stellar structures is physically acceptable, causal, and stable. The model inherently exhibits the quadratic equation of state that can be utilized to investigate the material composition and stellar structures of the observed compact stars.

Optimasi Kadar Ultimate dan Tingkat Kebasaan Bio-arang Limbah Kayu Durian sebagai Pembenah Tanah

Konversi biomassa melalui pirolisis menghasilkan bio-arang, bio-minyak dan gas. Pirolisis biomassa dipengaruhi oleh kondisi pirolisis seperti bahan baku dan suhu pirolisis. Tujuan dari penelitian ini adalah menganalisis kondisi optimum kadar ultimate (CHO) dan pH bio-arang berdasarkan ukuran partikel bahan baku limbah kayu durian dan suhu pirolisis sebagai pembenah tanah. Limbah kayu durian yang digunakan dalam penelitian ini berukuran diameter 0,17–0,42 mm; 0,42–1,00 mm; dan 1,00–2,83 mm, dengan variasi suhu pirolisis 350°C, 450°C, dan 550°C sebanyak tiga kali ulangan. Optimasi menggunakan metode Response Surface Methodology. Berdasarkan model kuadratik, didapatkan kadar karbon optimum bio-arang sebesar 81,78% dengan ukuran partikel bahan baku pada 2,09 mm dan suhu pirolisis 530,5oC. Kadar hidrogen optimum bio-arang sebesar 3,35% dengan ukuran partikel bahan baku 2,89 mm dan suhu pirolisis 547,4oC. Kadar oksigen optimum bio-arang sebesar 12,22% dengan ukuran partikel bahan baku 1,89 mm dan suhu pirolisis 529,5oC. pH optimum bio-arang sebesar 8,35 dengan ukuran partikel bahan baku 0,6 mm dan suhu pirolisis 521,8oC. Kondisi proses terbaik untuk menghasilkan kadar ultimate dan pH yang paling optimal berada pada range ukuran diameter bahan baku 0,6 mm–2,89 mm dan suhu pirolisis sebesar 521,8oC–547,4oC. The Optimization of Ultimate Levels and Basicity of Durian Wood Waste Biochar as Soil AmendmentAbstractBiomass conversion through pyrolysis produces biochar, bio-oil and gas. Pyrolysis of biomass is influenced by pyrolysis conditions such as raw materials and pyrolysis temperature. The purpose of this study was to analyze the optimum conditions for ultimate levels (CHO) and pH of biochar based on the particle size of the durian wood waste and the pyrolysis temperature as soil amendment. Particle sizes of durian waste were 0.17–0.42 mm; 0.42–1.00 mm; and 1.00–2.83 mm in diameter where pyrolysis temperatures were 350°C; 450°C; and 550°C. Optimization was used by the Response Surface Methodology method. Based on the quadratic model, the optimum carbon content of biochar was 81.78% with the particle size at 2.09 mm and the pyrolysis temperature of 530.5oC. The optimum hydrogen content of biochar was 3.35% with a particle size of 2.89 mm and a pyrolysis temperature of 547.4oC. The optimum oxygen content of biochar was 12.22% with a particle size of 1.89 mm and a pyrolysis temperature of 529.5oC. The optimum pH of biochar was 8.35 with a particle size of 0.6 mm and a pyrolysis temperature of 521.8oC. The most optimal ultimate levels and pH were in the diameter size range of 0.6 mm-2.89 mm and pyrolysis temperature of 521.8oC-547.4oC.

Production of quicklime from Ashaka limestone through calcination process

This study is on the production of quicklime from Ashaka limestone through calcination process. Effects of temperature, particle size and time on quicklime yield were determined. The experiment was carried out at temperatures of 800, 900, 1000, 1100 and 1200 0C, particle sizes of 80mm, 90mm, 100mm, 300mm and 425mm and times of 0.5hr, 1hr, 2hrs, 3hrs and 4hrs. Analyses of the results showed that quicklime was successfully produced from Ashaka limestone through the calcination process. Quadratic model adequately described the relationship between quicklime yield and calcination factors of temperature, particle size and time. Recorded model F-value of 134.35 implies that the model is significant. The predicted R² of 0.9597 is in reasonable agreement with the adjusted R² of 0.9844; the difference is less than the critical value of 0.2. Optimum yield of 73.48% was obtained at optima operating conditions; temperature of 1000 0C, particle size of 90 µm and time of 3 hrs.

Experimental Research on Key Factors Influencing the Expansion Performance of New Type Sealing Materials

To improve the borehole sealing effect, especially that of coal seam with low permeability and micro fissures, this paper takes the expansion rate of the sealing material as the response value and establishes the quadratic model embracing the expansion rate and various experimental factors by designing orthogonal experiments. The response surface is used to further determine the significance order of each key factor according to the expansion rate and adjust the admixture content to obtain the optimal ratio of the sealing material. For the research investigating a sealing material, the optimal ratio of the sealing material is obtained: the content of water reducing agent of 0.5%, the content of retarder of 0.04%, water-cement ratio of 0.8, and the content of expansion agent of 10%. At this time, the expansion rate reaches 3.136%. Besides, a scanning electron microscope is used to observe the microscopic morphology of the material. According to the scanning electron microscopy analysis of new borehole sealing materials, the surface of the new borehole sealing material shows no holes and possesses compactness; and a large amount of ettringite is formed on the surface of the hydration product of hardened cement slurry. The ettringite improves the expansibility of the material. The new sealing material provides a new idea for gas sealing, which is of great significance to improve the efficiency of borehole extraction, improve the utilization rate of resources, and prevent gas accidents.

Effects of process variables on the reactivity of slaked lime produced from Shuk quicklime

This is a research report of the effects of process variables on the reactivity of slaked lime produced from Shuk quicklime. It involved the calcination (at temperature of 1000 0C, particle size of 90 µm and time of 3 hrs) of Shuk limestone and subsequent slaking of its quicklime. The quicklime was characterized by x-ray diffractometer (XRD) and scanning electron microscopy (SEM) respectively to determine its mineral content and surface morphology respectively. Effects of process variables (quicklime/water ratio, particle size and time) on the reactivity of the slaked lime were determined. The reactivity was optimized using response surface methodology (RSM). The XRD analysis revealed calcite as the type mineral of the Shuk quicklime. The surface morphology of the quicklime sample showed that the particles are packed together in powdered form with visible pores that will allow passage of water. Reactivity of the lime was influenced by the quicklime/water ratio, particle size and time. Quadratic model appropriately explained the relationship between reactivity and considered slaking factors of quicklime/water ratio, particle size and time. The optimum reactivity value of the slaked lime was obtained as 59.3 oC at quicklime/water ratio of 0.24 g/ml, particle size of 88.2 µm and time of 15.1 minutes.

Processing of Yandev quicklime for potential amelioration of acidic soil

This study focused on processing of Yandev quicklime for potential amelioration of acidic soil. It involved production of quicklime from the Yandev limestone, characterization and slaking of the quicklime. In a batch process, 10g of the limestone (90mm particle size) was calcined for 3hrs to produce the quicklime. Mineralogical composition of the quicklime was determined by X-ray Diffractometer (XRD), while scanning electron microscope (SEM) was used to examine its surface morphology. The CaO was hydrated for the production of slaked lime (Ca (OH) 2). The slaking process was carried out by digesting CaO in distilled water. During the slaking/hydration process, values of reactivity (rise in temperature) were recorded. Central composite design (CCD) tool of Design Expert Software 11 was used to design the experiment of the slaking process. Quicklime/water ratio, particle size and time were the considered slaking variables, while reactivity was considered as the response. Analysis of the results quicklime is made up of pure calcite with visible pores. Quadratic model adequately described the relationship between reactivity and the considered slaking factors of quicklime/water ratio, particle size and time. Optimum reactivity was obtained as 58.4 0C with the corresponding optimal factors of quicklime/water ratio (0.26 g/ml), particle size (93.0 µm) and time (16.4 minutes). Properties of the slaked lime showed that it is suitable for acidic soil amelioration.