Development Newer Analytical Techniques for the Estimation of Benfotiamine and its Combination with Pyridoxamine Dihydrochloride and Resveratrol

INTRODUCTION: Analytical research is used to identify potential sources of safety problems in the products. The analytical effort required to provide this information can be divided into a number of analytical tasks which are as below, 1. Determination of identify, purity of starting materials and intermediates used in manufacturing the drug substance. 2 Isolation and identification of trace impurities in drug substance. 3. Determination of degradation rates and products. 4. Establishment of an analytical reference standard for the drug substance. The analytical methods require the meet crieterian like sensitivity, specificity, precise, robust and raggedness. The degrees of complexity acceptable in the analytical procedure vary considerably from task to task and therefore require a variety of analytical techniques to satisfy them. AIM AND OBJECTIVE: Benfotiamine is an antioxidant dietary supplement drug used in diabetic neuropathy. The US FDA approved benfotiamine in January 18, 2006 to diabetic neuropathy and benfotiamine in combination of pyridoxamine dihydrochloride and resveratrol. Literature reveals very few analytical techniques for the estimation of benfotiamine from tablets. Also there is no analytical method reported for the combination of benfotiamine with pyridoxamine dihydrochloride and resveratrol, till date. Hence the major objective of the present research work is, 1. To develop and validate UV spectroscopic method for the estimation of benfotiamine in bulk drug and tablet formulation. 2. To develop and validate stability indicating HPTLC method for the determination of benfotiamine and its application of accelerated stability studies of benfotiamine tablets. 3. To develop and validate a HPTLC method for estimation of benfotiamine in combination with pyridoxamine dihydrochloride and resveratrol in combined dosage from. 4. To develop a validated RP-HPLC method for estimation of benfotiamine in combination with pyridoxamine dihydrochloride and resveratrol tablet formulation. SUMMARY: In current research work newer analytical methods were developed and validated for benfotiamine in single dosage form and its combination with pyridoxamine dihydrochloride and resveratrol. An UV spectroscopy and stability indicating HPTLC methods were developed for the quantification of benfotiamine in single dosage form and for the estimation of benfotiamine in combined dosage form two chromatographic methods viz a HPTLC and HPLC were developed. Analytical methods for benfotiamine in single dosage form The development of UV spectrophotometric method involved scanning of the standard and sample solutions in the UV range using UV visible spectrophotometer. Benfotiamine showed maximum absorbance at 240nm. The method was validated for linearity, precision, accuracy and stability. An overly of different concentrations of benfotiamine was noted with absorbance at λmax. The linear concentration was 4-24μg/ml and the correlation value was 0.999. The percentage RSD values of repeatability, interday and intraday were found to be ˂ 2, which proves precision of the method. The drug solution was found to be stable up to 48hrs at room temperature. The method was the applied to estimation of Benfotiamine bulk drug and tablet formulation. For the estimation of Benfotiamine by HPTLC method, the sample solutions were applied on silica gel G60F254 TLC plates and the chromatogram was developed using mobile phase comprising of Glacial acetic acid : Methanol : Triethylamine ( 9: 1% v/v, 2drops) and detection was carried out at 275 nm using densitometer. The Rf value of Benfotiamine was 0.29±0.02, which showed linearity range from 0.1 – 0.6μg/spot and correlation coefficient 0.998. The percentage RSD values of repeatability, intraday and interday were found to be ˂ 2. It proves precision of the method. CONCLUSION: The UV, HPTLC and HPLC methods developed were validated as per ICH guidelines and found to be specific, accurate and precise. The results of all the methods were ascertained by statistical analysis. Among the two analytical methods developed, HPTLC is more sensitive technique, whereas UV is a simpler technique for the estimation of Benfotiamine in single dosage form. The HPTLC is more sensitive than HPLC method for the analysis of Benfotiamine in combination with Pyridoxamine dihydrochloride and Resveratrol. However HPLC offers a more reliable quantification than HPTLC for combination. All the four methods were successfully employed to analyse benfotiamine from single dosage form or in combination with Pyridoxamine dihydrochloride and Resveratrol. They would serve as good analytical tools for the quality control and research involving Benfotiamine and its combined dosage form with Pyridoxamine dihydrochloride and Resveratrol

MODEL COMPUTATION WITH SECOND-ORDER RADIATIVE TRANSFER EQUATION FOR SNOW MEDIUM USING COUPLED FINITE ELEMENT METHOD AND METHOD OF MOMENT AND RELAXED HIERARCHICAL EQUIVALENT SOURCE ALGORITHM

Active microwave remote sensing is essential to monitor the conditions of the environment by analyzing the microwave returns from the earth terrain. Various Computational Electromagnetics (CEM) techniques are implemented to study the backscattering coefficient of numerous earth terrains such as vegetation and snow medium. In this paper, a theoretical model based on second order radiative transfer equation is investigated by incorporating two computational methods which are known as coupled Finite Element Method (FEM) and Method of Moment (MoM), and Relaxed Hierarchical Equivalent Source Algorithm (RHESA). These theoretical models consider three shapes of scatterers which can be used to represent the ice particles of snow medium. These mentioned shapes are sphere, droxtal and hexagonal column. These methods are used to investigate the effect of various incident angles and frequencies on the backscattering mechanism. These results are compared with analytical Mie solution and ground truth measurement to analyze and verify the model

An Understanding of Behavior Difference as for Students and Workers Using Public Transits in Chongqing, China

Various studies on students or workers using public transits have been conducted. However, few studies consider behavior difference between them under same context. This study intends to determine factors influencing students and workers using different public transits for elastic travel on weekends in Chongqing, for a better understanding of behavior difference between the two typical travel population in cities. This study utilized the data from Chongqing Travel Survey in 2015 for analysis. Two set of binary logistic regression model were employed for significant factor determination. The results showed that travel expense and time walking to station were the collective significant factors influencing students and workers using public transits for elastic travel in Chongqing. However, gender and travel purpose only significantly influenced students using public transits for elastic travel in Chongqing, and time walking to destination and travel comfort only significantly influenced workers using public transits for elastic travel in Chongqing. Besides that, based on the model results, this study revealed the behavior difference of students and workers in Chongqing using public transits for elastic travel. And the researching findings in this study aimed at providing an original direction of thinking for public transits operators about differentiating with students and workers to balance the traffic resource between bus and rail transit. Keywords: Balance, Behavior Difference, Chongqing, Elastic Travel, Public Transit

Regulation of B cell linker protein transcription by PU.1 and Spi-B in murine B cell acute lymphoblastic leukemia

B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation-specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk. We hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes encoding tumor suppressors in the B cell lineage. Characterization of aging ΔPB mice showed that leukemia cells expressing IL-7R were found in enlarged thymuses. IL-7R-expressing B-ALL cells grew in culture in response to IL-7 and could be maintained as cell lines. Cultured ΔPB cells expressed reduced levels of B cell linker protein (BLNK), a known tumor suppressor gene, compared with controls. The Blnk promoter contained a predicted PU.1 and/or Spi-B binding site that was required for promoter activity and occupied by PU.1 and/or Spi-B as determined by chromatin immunoprecipitation. Restoration of BLNK expression in cultured ΔPB cells opposed IL-7-dependent proliferation and induced early apoptosis. We conclude that the tumor suppressor BLNK is a target of transcriptional activation by PU.1 and Spi-B in the B cell lineage. Copyright © 2012 by The American Association of Immunologists, Inc

Mesospheric Gravity Waves Observed Near Equatorial and Low-Middle Latitude Stations: Wave Characteristics and Reverse Ray Tracing Results

Gravity wave signatures were extracted from OH airglow observations using all-sky CCD imagers at four different stations: Cachoeira Paulista (CP) (22.7° S, 45° W) and São João do Cariri (7.4° S, 36.5° W), Brazil; Tanjungsari (TJS) (6.9° S, 107.9° E), Indonesia and Shigaraki (34.9° N, 136° E), Japan. The gravity wave parameters are used as an input in a reverse ray tracing model to study the gravity wave vertical propagation trajectory and to estimate the wave source region. Gravity waves observed near the equator showed a shorter period and a larger phase velocity than those waves observed at low-middle latitudes. The waves ray traced down into the troposphere showed the largest horizontal wavelength and phase speed. The ray tracing results also showed that at CP, Cariri and Shigaraki the majority of the ray paths stopped in the mesosphere due to the condition of m2\u3c0, while at TJS most of the waves are traced back into the troposphere. In summer time, most of the back traced waves have their final position stopped in the mesosphere due to m2\u3c0 or critical level interactions (|m|→∞), which suggests the presence of ducting waves and/or waves generated in-situ. In the troposphere, the possible gravity wave sources are related to meteorological front activities and cloud convections at CP, while at Cariri and TJS tropical cloud convections near the equator are the most probable gravity wave sources. The tropospheric jet stream and the orography are thought to be the major responsible sources for the waves observed at Shigaraki

Pathological Characteristics of Primary Bladder Carcinoma Treated at a Tertiary Care Hospital and Changing Demographics of Bladder Cancer in Sri Lanka

Objectives. The aim was to compare demographics and pathological features of bladder carcinoma treated in a urology unit with findings of previous studies done in Sri Lanka. Materials and Methods. Data of newly diagnosed patients with bladder cancer in a tertiary referral centre from 2011 to 2014 were analysed. Data on bladder cancers diagnosed from 1993 to 2014 were obtained from previous publications and Sri Lanka Cancer Registry. Results. There were 148 patients and mean age was 65 years. Male to female ratio was 4.1 : 1. Urothelial carcinoma (UC) was found in 89.2% of patients. Muscle invasion was noted in 35% of patients compared to 48.4% two decades ago. In patients with UC, 16.5% were found to have pT1 high grade tumour. It was 5.3% from 1993 to 2000. Pure squamous cell carcinoma was found in 8.1% of patients while primary or de novo carcinoma in situ (not associated with high grade pT1 tumours) was seen in one patient only. Conclusions. The percentage of squamous carcinoma is higher among Sri Lankan patients while primary carcinoma in situ is a rarity. The percentage of muscle invasive disease has decreased while the percentage of pT1 high grade tumours has increased during the last two decades in Sri Lanka

Sexto reporte de eventos adversos con tratamientos biológicos en Argentina. Informe del registro BIOBADASAR

Objetivo: actualizar los resultados del registro BIOBADASAR sobre seguridad, duración y causas de interrupción del tratamiento luego de 8 años de seguimiento. Métodos: BIOBADASAR es un registro de seguridad de terapias biológicas establecido por la Sociedad Argentina de Reumatología. Se presenta la descripción de BIOBADASAR 3.0, una cohorte compuesta por 53 centros de Argentina seguidos prospectivamente desde agosto de 2010 hasta enero de 2018

Size Analysis of Higher-Order Functions

Contains fulltext : 92345.pdf (publisher's version ) (Open Access)TFP 2011 : 12th International Symposium on Trends in Functional Programming (TFP2011). Madrid, Spai