Design and evaluation of floating drug delivery systems of Metformin with natural gums as release retarding polymers

Metformin hydrochloride floating tablets were prepared by wet granulation method by using optimized concentrations of gas generating agents, binding agents and natural gums as polymers like gum kondagogu and gum karaya. The formulations F1-F4 with concentrations 2-3.5% were prepared to optimize binding agent and formulations F5-F7 with concentrations 15-20% to optimize gas generating agent where optimum percentage of binding agent was found around 2.3% and gas generating agent was found around 17.25% to get quick floating lag time. The prepared granules evaluated for various parameters showed good results in which the Carrs index, hausner ratio and angle of repose, the values were found in between 9.05-16.78, 1.02-1.46 and 23.17-32.64 respectively. All compressed formulations were evaluated for various parameters and results of hardness, friability, drug content, were found around 7.1-8.8kg/cm2, 0.56-1.48% and 499.3-499.8mg respectively. The tablets prepared by these granules of two natural gums as polymers showed desired floating properties. F6 formulation containing gum kondagogu and F11 formulation containing gum karaya showed good release retardation with release 99.42% and 99.75% respectively after 12 hours in in vitro drug release studies. Formulations F6 and F11 after stability studies showed good results proving stable. In vivo studies also showed good correlation with the results of in vitro and X-ray pictograms proved the formulations is stable in vivo. Formulations F6 and F11 contains natural gums Kondagogu and karaya with 17.25% concentration were considered as best formulation as they showed good release retardation and, in release kinetic studies the n-value found appropriate for controlled release formulations

H-1 NMR study of molecular dynamics and phase transitions in (CH3NH3) 2PbBr6 and [N(CH3)(4)](2)SeCl6.

The proton spin-lattice relaxation time (T-1) has been measured in methylammonium hexabromoplumbate, (CH3NH3)(2)PbBr6, in the range 77-450K and tetramethylammonium (TMA) hexachloroselenate, [N(CH3)(4) ](2)SeCl6 in the range 77-430K In (CH3NH3)(2)PbBr6, T-1 shows a slope change at 415K, a minimum at 215K, and a discontinuous jump at 167K In [N(CH3)(4)](2)SeCl6, T-1 shows a slope change at 340K and goes through a narrow symmetric minimum at 194K. Further, it exhibits a shoulder-like structure at 106K and goes through a broad minimum at 85K. Motional parameters such as activation energy and preexponential factor have been evaluated for the reorientational motion of CH3-NH3 groups and the TMA ion in different phases

Probabilistic Modeling of Ceramic Matrix Composite Strength

Uncertainties associated with the primitive random variables such as manufacturing process (processing temperature, fiber volume ratio, void volume ratio), constituent properties (fiber, matrix and interface), and geometric parameters (ply thickness, interphase thickness) have been simulated to quantify the scatter in the first matrix cracking strength (FMCS) and the ultimate tensile strength of SCS-6/RBSN (SiC fiber (SCS-6) reinforced reaction-bonded silicon nitride composite) ceramic matrix composite laminate at room temperature. Cumulative probability distribution function for the FMCS and ultimate tensile strength at room temperature (RT) of (0)(sub 8), (0(sub 2)/90(sub 2), and (+/-45(sub 2))(sub S) laminates have been simulated and the sensitivity of primitive variables to the respective strengths have been quantified. Computationally predicted scatter of the strengths for a uniaxial laminate have been compared with those from limited experimental data. Also the experimental procedure used in the tests has been described briefly. Results show a very good agreement between the computational simulation and the experimental data. Dominating failure modes in (0)(sub 8), (0/90)(sub s) and (+/-45)(sub S) laminates have been identified. Results indicate that the first matrix cracking strength for the (0)(sub S), and (0/90)(sub S) laminates is sensitive to the thermal properties, modulus and strengths of both the fiber and matrix whereas the ultimate tensile strength is sensitive to the fiber strength and the fiber volume ratio. In the case of a (+/-45)(sub S), laminate, both the FMCS and the ultimate tensile strengths have a small scatter range and are sensitive to the fiber tensile strength as well as the fiber volume ratio

Stochastic-Strength-Based Damage Simulation of Ceramic Matrix Composite Laminates

The Finite Element Analysis-Micromechanics Analysis Code/Ceramics Analysis and Reliability Evaluation of Structures (FEAMAC/CARES) program was used to characterize and predict the progressive damage response of silicon-carbide-fiber-reinforced reaction-bonded silicon nitride matrix (SiC/RBSN) composite laminate tensile specimens. Studied were unidirectional laminates [0] (sub 8), [10] (sub 8), [45] (sub 8), and [90] (sub 8); cross-ply laminates [0 (sub 2) divided by 90 (sub 2),]s; angled-ply laminates [plus 45 (sub 2) divided by -45 (sub 2), ]s; doubled-edge-notched [0] (sub 8), laminates; and central-hole laminates. Results correlated well with the experimental data. This work was performed as a validation and benchmarking exercise of the FEAMAC/CARES program. FEAMAC/CARES simulates stochastic-based discrete-event progressive damage of ceramic matrix composite and polymer matrix composite material structures. It couples three software programs: (1) the Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC), (2) the Ceramics Analysis and Reliability Evaluation of Structures Life Prediction Program (CARES/Life), and (3) the Abaqus finite element analysis program. MAC/GMC contributes multiscale modeling capabilities and micromechanics relations to determine stresses and deformations at the microscale of the composite material repeating-unit-cell (RUC). CARES/Life contributes statistical multiaxial failure criteria that can be applied to the individual brittle-material constituents of the RUC, and Abaqus is used to model the overall composite structure. For each FEAMAC/CARES simulation trial, the stochastic nature of brittle material strength results in random, discrete damage events that incrementally progress until ultimate structural failure

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Isolation and characterization of bioactive moiety from leaf extract of ipomoea mauritiana and evaluation of anti-inflammatory activity by Carrageenan induced rat paw edema test

Ipomoea mauritiana Jacq. is a member of family Convolvulaceae and commonly called as Ksheervidari is widely used in various traditional medicines for the treatment of many diseases. In the present work the column fractions of leaf extracts of I. mauritiana obtained by Soxhlet exrtaction was subjected to TLC, column chromatography, HPLC and liquid chromatography and mass spectroscopy (LC-MS). The compounds like caffeic acid and β-amyric acetate were tentatively identified to be present in one of the purified fraction. The column fraction was also tested for anti-inflammatory activity by carrageenan induced rat paw edema assay. The column fraction tested showed a very good anti inflammatory activity

Evaluation of the Mechanical Properties of Solid Oxide Fuel Cell Materials

Thesis (Master's)--University of Washington, 2019In the pursuit of economic sources of “green energy”, Solid Oxide Fuel Cells (SOFCs) are of substantial interest due to their high efficiency, long-term stability, low emissions, and relatively low costs. With a capability of achieving an efficiency of 80%, SOFCs are the most efficient of all the hydrogen fuel cells. These systems operate at high temperatures, often ranging between 500°C and 1000°C. Due to such high operating temperatures, the components of SOFCs are fabricated from ceramic or cermet materials, which exhibit high sensitivity to pores and flaws. Hence, it is important to characterize the reliability and service life of advanced ceramic components at extreme operational environments. Due to their relatively high flaw sensitivity, the mechanical properties of ceramics should be described in a probabilistic manner, to enable a complete description of component reliability. Magnesia Magnesium Aluminate (MMA) is a candidate ceramic material for high-temperature applications including SOFCs. In the present investigation, the strength distribution and Slow Crack Growth (SCG) behavior of a dense MMA manifold material and porous MMA tube material were evaluated via 4-point flexural testing at temperatures of 20°C, 50°C, and 850°C under wide range of environmental conditions involving exposure to moisture and a mixture of hydrogen and nitrogen gas. A fractographic analysis was performed to identify the origins of failure and as a function of the environment and temperature. It was found that the flexure strength distribution for the dense MMA (proposed as a manifold material) exhibited a Weibull modulus of approximately 11. In addition, at 50°C and 3.5% moisture by volume, the strength displayed significant rate dependence with an SCG exponent of 17, indicating relatively high susceptibility of the material to slow crack growth failures. The flexure strength distribution of the porous MMA (proposed as a tube material) exhibited a Weibull modulus of approximately 10, with large difference between the ambient conditions and high temperature response. At 850°C and within a reformulated fuel environment (50% moisture, 45% nitrogen and 5% hydrogen by volume) the strength displayed significant rate dependence with a SCG exponent of -33, indicating susceptibility of the material to slow crack growth failures. Thermal cycling was found to increase the Weibull modulus of both the dense MMA manifold materials and porous MMA tube materials. Fractography showed that regardless of loading rate or environment, large surface pores resulting from processing were the origins of failure in the weakest samples of both the manifold and tube MMA materials. The results from this investigation should make a significant contribution to the literature concerning the high temperature behavior of structural ceramics

Proton NMR Study of Molecular Dynamics and Phase Transitions in Trimethyl Ammonium Hexachloro Plumbate [NH(CH3)3]2PbCl6{[NH{(CH_3)}_3]}_2PbCl_6 and Tetramethyl Ammonium Hexachloro Plumbate [N(CH3)4]2PbCl6{[N{(CH_3)}_4]}_2PbCl_6

The proton spin lattice relaxation time $(T_1)$ measured as a function of temperature in the range 424 to 119 K in trimethyl ammonium hexachloro plumbate $[(TrMA)_2PbCl_6]$ shows phase transitions at 340 and 119 K. The observed badly resolved minima in this compound are explained on the basis of C3 reorientations of inequivalent trimethyl ammonium and methyl groups. The computed second moment values, suggest the freezing of both types of reorientation around 117 K. Proton $T_1$ studies in tetramethyl ammonium hexachloro plumbate $[(TMA)_2PbCl_6]$ in the temperature range 295 to 106 K shows a deep $T_1$ minimum at 180 K and a shallow one around 111 K, which are interpreted in terms of inequivalent tetramethyl ammonium (TMA) ions as well as $CH_3$ reorientation