VALIDATED COLORIMETRIC METHODS FOR THE ESTIMATION OF TENELIGLIPTIN IN TABLETS

Two simple sensitive and precise methods A and B were developed for the estimation of teneligliptin in bulk drug as well as in pharmaceutical dosage form. Method A is based on the formation of a red colored chromogen by reaction of teneligliptin with potassium thiocyanate in presence of ferric chloride, which has an absorption maximum at 554nm.   Method B is based on the formation of an orange colored complex by complexation reaction of teneligliptin with 2, 2’- bipyridyl in the presence of ferric chloride which has an absorption maximum at 421nm. The proposed methods are statistically validated and found to be useful for the routine determination of teneligliptin in tablets. Keywords: Teneligliptin, Colorimetry, Tablets, ValidationÂ

A study of methodologies and critical parameters associated With co2 storage estimation in deep saline aquifers

Deep saline aquifers have greater potential for carbon dioxide (CO2) storage (around 12,000 Gt global capacity) than alternative storage media and could be adopted anywhere in the world. It is important to understand methodologies for the estimation of CO2 storage capacities in relation to different trapping mechanisms and the extent to which critical parameters such as aquifer thickness, porosity, salinity and permeability are taken into account. Storage security will improve over time, especially as a result of mineral trapping. This paper reviews methods of estimating CO2 storage potential from earlier studies and numerically estimates the storage potential in saline aquifers considering critical parameters such as saline aquifer and porosity

Influence of long-range dipolar interactions on the phase stability and hysteresis shapes of ferroelectric and antiferroelectric multilayers

Phase transition and field driven hysteresis evolution of a two-dimensional Ising grid consisting of ferroelectric-antiferroelectric multilayers that take into account the long range dipolar interactions were simulated by a Monte-Carlo method. Simulations were carried out for a 1+1 bilayer and a 5+5 superlattice. Phase stabilities of components comprising the structures with an electrostatic-like coupling term were also studied. An electrostatic-like coupling, in the absence of an applied field, can drive the ferroelectric layers towards 180º domains with very flat domain interfaces mainly due to the competition between this term and the dipole-dipole interaction. The antiferroelectric layers do not undergo an antiferroelectric-to-ferroelectric transition under the influence of an electrostatic-like coupling between layers as the ferroelectric layer splits into periodic domains at the expense of the domain wall energy. The long-range interactions become significant near the interfaces. For high periodicity structures with several interfaces, the interlayer long-range interactions substantially impact the configuration of the ferroelectric layers while the antiferroelectric layers remain quite stable unless these layers are near the Neel temperature. In systems investigated with several interfaces, the hysteresis loops do not exhibit a clear presence of antiferroelectricity that could be expected in the presence of anti-parallel dipoles, i. e., the switching takes place abruptly. Some recent experimental observations in ferroelectric-antiferroelectric multilayers are discussed where we conclude that the different electrical properties of bilayers and superlattices are not only due to strain effects alone but also long-range interactions. The latter manifests itself particularly in superlattices where layers are periodically exposed to each other at the interfaces

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Influence of thermal treatment on mode I fracture toughness of certain Indian rocks

An experiment was carried out to measure the static mode I fracture toughness of Manoharpur sandstone, Bellary dolerite and Dholpur sandstone after thermal treatment at different temperatures that ranged from ambient conditions to 600 degrees C. The three-point bending method was applied using cracks straight through semi-circular bending (CSTSCB) specimens that were fabricated according to International Society for Rock Mechanics (ISRM) standards. Three different rocks were used to measure the degree of influence of thermal treatment on fracture toughness in different rocks. In addition, petrographic and X-ray diffraction (XRD) analyses were carried out to identify the compositions of these rocks. Finally, scanning electron microscope (SEM) analysis was performed in order to measure the micro-cracks that were induced within these rocks as a result of thermal treatment. The experimental results demonstrated that, up to a temperature range of 100 degrees C, the fracture toughness of Manoharpur sandstone, Bellary dolerite and Dholpur sandstone increased by 40%, 25% and 65%, respectively, when compared to the ambient condition, and thereafter decreased with a gradual increase"of temperature. At 600 degrees C, when compared to the ambient condition, the fracture toughness of these rock types decreased by 59%, 36% and 30% for Manoharpur sandstone, Bellary dolerite and Dholpur sandstone, respectively. (C) 2016 Elsevier B.V. All rights reserved

CO2 permeability of Indian bituminous coals: Implications for carbon sequestration

The permeability of coal is one of the most critical parameters in estimating the performance of coal seams as methane reservoirs or carbon dioxide sinks. The reservoir behaviour of coal offers many challenges for the long-term planning of gas production performance and the drainage of water from reservoirs. Moreover, heterogeneity in coal from basin to basin, from seam to seam and within parts of the same seam makes the process more complex. Reservoir-specific understanding is needed for the best possible estimation of its behaviour. Factors such as shrinkage/swelling of coal matrix, gas flow and slippage, geomechanical changes, cleat anisotropy and effective stresses control the flow behaviour of gases in coal. Studies of these aspects have gathered momentum in recent decades for different basins across the world. However, no research is available on swelling-induced permeability characteristics or the role of effective stresses for Gondwana coals in India. Considering the fairly high CO2 storage potential of Indian coals, bituminous coals of the Barakar Formation in Jharia basin, India were tested using gas phase CO2 under triaxial conditions. This paper presents the results of changing effective stresses, in terms of confining stresses and pore pressure, incorporating the role of coal swelling with time on the flow pattern of gaseous CO2. Corresponding to different depths of target coal seams, coal was subjected to different confining stresses in a newly-developed triaxial cell. For each confinement, CO2 was injected at different injection pressures. To minimize the effects of temperature on the characteristics of the gas phase, it was kept constant at 26 degrees C throughout, while use of the drained method of testing maintained the downstream pressure equal to one atmosphere. The results showed that at low confinement, increase in gas injection pressures leads to an initial decrease in permeability of coal, which then becomes almost constant. However, at higher confinements, the permeability increases with increasing injection pressure. Swelling in coal contributes to reduction of permeability. The volumetric expansion in coal reduces the permeability with changing gas injection pressure during the initial confinement. As the confining pressure is increased, coal permeability reduces by one to two orders of magnitude. Finally, an empirical relation accounting for the role of effective stresses and swelling on coal permeability is proposed for Indian coals. At lower effective stresses, the logarithmic decline model is better suited, while the exponential decline relationship fits the data better at effective stresses >12 MPa. (C) 2012 Elsevier B.V. All rights reserved

Laboratory Simulation of Flow through Single Fractured Granite

Laboratory simulation on fluid flow through fractured rock is important in addressing the seepage/fluid-in-rush related problems that occur during the execution of any civil or geological engineering projects. To understand the mechanics and transport properties of fluid through a fractured rock in detail and to quantify the sources of non-linearity in the discharge and base pressure relationship, fluid flow experiments were carried out on a cylindrical sample of granite containing a 'single rough walled fracture'. These experiments were performed under varied conditions of confining pressures, sigma (3) (5-40 MPa), which can simulate the condition occurring about 1,000 m below in the earth crust, with elevated base pressure, b (p) (up to 25 MPa) and by changing fracture roughness. The details of the methodologies involved and the observations are discussed here. The obtained results indicate that most of the data in the Q verses b (p) plot, fall on the straight line and the flow through the single fracture in granite obeys Darcy's law or the well-known "cubic law" even at high value of b (p) (=4 MPa) and sigma (3) (=5 MPa) combination. The Reynolds number is quite sensitive to the b (p), sigma (3) and fracture roughness, and there is a critical b (p), beyond which transition in flow occurs from laminar to turbulent. It is believed that such studies will be quite useful in identifying the limits of applicability of well know 'cubic law', which is required for precise calculation of discharge and/or aperture in any practical issues and in further improving theoretical/numerical models associated with fluid flow through a single fracture

High heat generating granites of Saudi Arabian shield: Prospect for CO2 emissions reduction and climate mitigation

Countries such as Saudi Arabia are experiencing island heat effect due to large consumption of fossil fuels. The ambient temperature in the cities of Saudi Arabia is increasing faster than the global average due to this effect. The recorded temperature over the past decade has shown an anomalous increase of 0.76 C (IEA, 2013b, Almazroui et al., 2012). Besides such temperature anomalies, Saudi Arabia experiencing flash floods in the recent past. All such abnormal weather pattern is apparently attributed to the large volumes of carbon dioxide (CO2) emissions from domestic and industrial sectors. With the country having greater than 3000 CDD (Cooling Degree Days), more than 80% fossil fuel energy (192 TWh) is spent for space cooling (IEA, 2013, a, b) and by the year 2020 this quantity is expected to exceed 605 TWh (EIA, 2013). The per capita electricity consumption is crossing 8500 kWh (WB, 2012, IEA, 2012). Nearly 446000 Gg of CO2 is being emitted from fossil fuel combustion, while CO2 emissions from electricity and heat production is of the order of 181000 Gg. Manufacturing industries also emit similar amount of CO2. Apparently the micro-weather anomalies are caused due to such large CO2 emissions. The country however has options to implement CDM (clean development mechanism) by reducing CO2 emissions and stabilize its micro-weather anomalies by using hydrothermal and hot dry rock resources (EGS). The country’s EGS potential is enormous compared to hydrothermal resources (Fig. 1). High heat generating granites in the Arabian shield occupy an area of about 161 500 km2 and the heat generating capacity of the granites vary from 8 to 134 µW/m3. These granites are under severe NE-SW Compressional regime due to the active Red Sea mid ocean ridge. Thus these granites are the best candidates to initiate EGS projects. Experimental investigation to understand the fracture propagation under confined stress conditions are in progress