Aim: A simple and economic method was developed as a derivative spectrophotometric study for estimation of evogliptin tartrate in the tablet dosage form. The developed derivative method was validated as per the ICH guideline. Materials and Methods: The maximum absorption of evogliptin tartare was found to be 267 nm and its first and second derivative wavelengths were measured at 275 nm and 277 nm respectively. Water was used as a solvent for all measurements. Results: The developed method was shown linear in the concentration range of 20-120 mu g/ml for evogliptin tartrate and shows a good correlation coefficient. The precision of the developed method was less than the maximum allowable limit (% RSD < 2) specified by the ICH guidelines. Excellent % recovery (98% -101%) with less than 2% RSD value indicates method was accurate. Conclusion: The developed UV - Visible method was simple eco-friendly, precise and accurate as per ICH guidelines. The proposed method will use in quality control for routine analysis of evogliptin tartrate in the pharmaceutical dosage form.

Background A quality by design approach can potentially lead to a more robust/rugged method development due to emphasis on the risk assessment and management. By carefully understanding the step-by-step procedure for analytical QbD-based optimization parameters, such as analytical target profile and critical quality attributes (CQAs), was assessed. The present study describes the simple, rapid, sensitive and cost-effective RP-HPLC method development and validation for the estimation of evogliptin tartrate in pharmaceutical dosage form. Results The factor screening studies were performed using Box–Behnken design by three key components of the RP-HPLC method (mobile phase, pH and flow rate). The chromatographic conditions were optimized with the Design Expert software trial version 13.0. The optimal chromatographic separation was achieved having water C18 column (250 mm × 4.6 mm, 5 μ) and using mobile phase as a methanol and phosphate buffer (pH 4.5) 60:40% v/v with a flow rate 1.0 ml/min and UV detection at 267 nm. The Box–Behnken experimental design describes the interrelationship of mobile phase, pH and flow rate at three different levels, and responses of retention time and tailing factor were observed with response surface plot and statistical data. The developed method was validated as per recommended ICH guidelines which revealed the high degree of linear, precise, accurate, sensitive and robust method over the existing RP-HPLC method for evogliptin tartrate. Conclusion The developed QbD-based method helped in generating a design space and operating space with knowledge of all method performance characteristics, and RP-HPLC method takes less time and can be used in the industry for routine quality control of bulk and marketed formulation of evogliptin tartrate.

The objective of this study is to develop simple, rapid and sensitive reversed-phase high performance liquid chromatography method for bilastine in tablet dosage form by quality by design approach. In reversed-phase high performance liquid chromatography method, chromatographic conditions such as mobile phase composition and flow rate were optimized with the help of Design-Expert software using central composite design. In this method, bilastine was estimated using octadecylsilane column (250x4.6 mm, 5 mu m) and methanol:acetonitrile (90:10 % v/v) as mobile phase and flow rate 1 ml/ min which are optimized using Design-Expert software. Method was developed at 280 nm detection wavelength. The retention time was found to be 3.484 min. The proposed method was successfully applied to the determination of bilastine in tablet dosage form. High linearity of developed method was confirmed over concentration range of (20-120) mu g/ml and correlation co-efficient is 0.9997. The percentage relative standard deviation for precision and accuracy of the method was found to be <2 %. The recovery was in the range of 98.8 %-99.7 %; limit of detection was found to be 0.1352 g/ml and limit of quantification was found to be 0.4098 mu g/ml. Bilastine was found to degrade under oxidation condition. There was no interference of excipient and degradation product in retention time, so the method was specific. Analytical parameters such as precision, accuracy, limit of detection, limit of quantification and robustness were determined according to International Conference on Harmonization guidelines.

Objective: The objective of the work was to develop a simple suitable spectrophotometric method for estimation of Teriflunomide in Pharmaceutical dosage forms. Method: Simple UV Spectrophotometric methods was developed for estimation of Teriflunomide in pharmaceutical dosage form by measuring absorbance at maximum at 200 – 400 nm. The method has been validated as per ICH guidelines. Result and discussion: UV Spectrophotometric method showed good linearity from 2-12 μg/mL the method has been validated as per ICH guidelines. Accuracy (% recovery) for zero order (101.46%-99.93 %) and for first order (101.56%-99.72%). The limit of detection (LOD) for zero order was found to be 0.565μg/mL and for first order was found to be 0.816 μg/mL while the limit of Quantitation (LOQ) for zero order was found to be 1.713μg/mL and for first order was found to be 2.472 μg/mL. Conclusion: The developed Spectrophotometric methods were validated as per ICH guideline and can be used for routine analysis of Teriflunomide in Pharmaceutical dosage form.

The CROPGRO-pigeonpea model embedded in DSSAT v4.7.5 was used to assess the impact of climate change on phenology and grain yield of reference genotype of different pigeonpea maturity groups. The impact of climate change delayed reproductive stages (anthesis, maturity) and decreased grain yield of reference genotype of different pigeonpea maturity groups were evident in all scenarios. Short duration genotypes (MN5, ICPL88039, Prabhat, UPAS120) showed progressively higher decrease in yield as compared to medium (Maruti, Asha, ICP7035) and long (Bahar, MAL13) duration genotypes with each successive increase in scenatio from RCP2.6 to RCP8.5 and projected year from 2010 to 2095. Anthesis was delayed 9 days in MN5 to 20 days in Bahar and maturity delayed 15 days in MN5 to 24 days in Bahar with RCP 8.5 in year 2095 in comparison to RCP2.6 in years 2010, whereas, grain yield was decreased 14% in Bahar to 66% in MN5 among genotypes of different maturity groups.

A new simple, rapid, accurate and precise method for estimation of Bilastine in pharmaceutical dosage form by reverse phase liquid chromatography. The developed method employed mobile phase was Acetonitrile and Ammonium acetate pH 5.0 adjusted with glacial acetic acid with 85:15% v/v and flow rate 1.0ml/min. Method was developed using column C18 Water (150 × 4.6mm, 5µm) and detection wavelength was 215nm. The retention time was found to be 2.519 min. the proposed method was successfully applied to the determination of Bilastine in dosage form. High linearity of developed method was confirmed over concentration range of 25- 150 µg/ml and co-relation co-efficient is 0.996. The percentage RSD for precision and accuracy of the method was found to be less than 2%. The recovery was in the range of 99 – 102% and limit of detection was found to be 0.45µg/ml and limit of quantification was found to be 1.20µg/ml. Bilastine was found to degrade under acid and oxidation conditions. There was no interference of excipient and degradation product in retention time so method was specific. Analytical parameter such as precision, accuracy, limit of detection, limit of quantification and robustness were determined according to international Conference on Harmonization (ICH) guidelines.

INTRODUCTION:Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at the H1 receptor and prevent binding of histamine at the H1 receptor, thereby preventing allergic reactions. Molecules containing a triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with the H1 receptor.METHODS:Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe-432 subunits. A pharmacophore model, new 5-(4-substituted phenyl)-4-(phenylamino)-4-H-1,2,4-triazole-3- thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum.RESULTS:According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to easily penetrate cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others.CONCLUSION:Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum, taking chlorpheniramine maleate as a standard. Most of the compounds were found to possess better antihistamine activity.

A major subset of IL-10 secreting B-cells, commonly characterized as CD19+/38hi/24hi, encompass B-regulatory cells (B-regs). We report effects of changes in stimulating molecule concentration on population of Interleukin-10 secreting B-regs of human origin. B-regs may be obtained from in-vitro co-culture of adipose tissue derived mesenchymal stromal cells (AD-MSC) and peripheral blood mononuclear cells (PBMC) for potential cell therapy. Lipopolysaccharide–E.coli-K12 strain (LPS-EK) was added in varying concentrations in the co-culture of AD-MSC and peripheral blood mononuclear cells (PBMC). At each time point, IL-10 concentration of cell supernatant was estimated by quantitative ELISA. Morphology, sterility, total count, viability and immune-phenotype of cells were determined. We analyzed the data to determine the time interval at which maximum B-reg population and optimum secretion of IL-10 was obtained. The present study provides precious information about the in vitro dynamics of IL-10 secretion by human B-regs generated from AD-MSC and PBMC. The present study focuses on in vitro generation of B-regs from adipose tissue derived mesenchymal stromal cells (AD-MSC) and peripheral blood mononuclear cells (PBMC), as well as on partial characterization of B-regs in terms of amount of IL-10 secreted, time taken and amount of stimulating molecule (i.e. LPS-EK) required for optimum IL-10 secretion. It has been reported that B-regs secrete cytokine in trace quantities. The medium which is added for feeding the cells further dilutes the secreted cytokines by many folds. In our study, the samples were appropriately concentrated, so that the cytokines could be detected by quantitative Enzyme Linked Immunosorbent Assay (ELISA).

GFLD-CM3 model was used to generate weather data under RCPs scenario i.e. RCP 2.6, 4.5, 6.0 and 8.5 for years 2010, 2035, 2065 and 2095 for Varanasi, Uttar Pradesh. The generated data were used to assess the impact of climate change on phenology and yield of wheat crop using CERES-Wheat model. The results revealed that the impact climate change hastened reproductive stages (anthesis, maturity) and decreased yield in all scenarios. The impact was highest under RCP 8.5. Days to antheis and days to maturity were projected to reduce by 22 days and 24 days, respectively in 2095 whereas, grain yield decreased by 61.0 per cent.

Aim: B-regulatory cells (B-regs), commonly characterized as CD19+/38hi/24hi, comprise of a major subset of IL-10 secreting B-cells. We report optimization of culture conditions for B-regs of human origin, obtained from in-vitro co-culture of donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy.Material and methodology: Five sets of 6-well plates were filled with proliferation media. Each plate was seeded with 5 × 104 ADMSC and 1 × 106 cells of responder and stimulator peripheral blood mononuclear cells (PBMC) and incubated at 37˚C, 5% CO2 after addition of lipopolysaccharide–E.coli-K12 strain (LPSEK) in varying concentrations. At each time point, one plate was withdrawn and contents centrifuged. IL-10 concentration of cell supernatant was estimated by quantitative ELISA. Pellet was resuspended to determine morphology, sterility, total count, viability and immunophenotype of cells.Results: The highest B-reg population (0.19×106 cells/ml) was noted at 24 hours with 400 ng/ml LPS-EK, which also correlated with optimum secretion of IL-10 (1.58 pg/ml), for the same time interval.Conclusion: The present study provides valuable information about the dynamics of IL-10 secretion by in vitro generated human B-regs, obtained from donor AD-MSC and recipient PBMC.

Introduction: This research focuses on development and optimization of dipyridamole (DPM) gastroretentive (GR) floating matrix tablets through risk-based approach using combination of rate controlling hydrophilic polymers. Materials and Methods: A 32 full factorial design was deployed to optimize ratio of polymers and polymer concentration in the formulation. Dissolution studies, Buoyancy studies, swelling index studies, kinetic modelling, drug content, and differential scanning calorimetry studies were performed to effectively assess developed gastroretentive dosage form. Estimation of related substances was also done for optimized formulations to check the stability of dosage form during shelf life. Results and Discussion: Buoyancy studies suggested that concentration of PanExcea T GR polymer should be at least 25% w/w or more to get better floating and swelling capabilities if used alone as rate controlling polymer. Selection of optimum batches was done using constraintbased graphical optimization technique. The optimum batches exhibited desired extended drug dissolution profile, minimal floating lag time, and total floating time of > 12 h. Thermal characterization studies also preclude any drug polymer interaction and change in polymorphic form of drug during manufacturing process. Stability studies indicated optimized formulations are stable under selected packaging configurations. Conclusion: The present research exemplifies successful application of quality by design approach in designing gastroretentive dosage form of DPM. From the present study, it can be concluded that selection of appropriate ratio and concentration of hydrophilic polymers play a pivotal role in matrix integrity, buoyancy, swelling potential as well as drug release profile of GRDDS.

Despite the extensive advancements in the field of drug delivery, the oral route remains the favorable route for administration of therapeutic actives. A success of oral controlled drug delivery systems is associated with reduced dosing frequency, decreased fluctuation in plasma drug concentration profile along with improved patient compliance. However, they are also associated with challenges like shorter gastric residence time, unpredictable gastric emptying and poor bioavailability for some molecules. This has initiated tremendous advancements in the field of gastro-retention to achieve controlled release of drugs along with improved bioavailability of drugs with narrow absorption window as well as localized action in the stomach and upper part of GIT. In present review, efforts have been envisaged to summarize our current understanding in the field of gastro-retention and their in vitro as well as in vivo characterization. Present review also highlights commercially utilized gastro-retentive technologies and some recently granted US patents in the field of GRDDS.

The aim of this study is to compare the efficacy and safety of combination containing Atorvastatin plus Fenofibrate (ATO+FENO) and to determine whether combination of Fenofibrate had clinically significant benefit over Atorvastatin alone (ATO) in patients with Hyperlipidemia.This is a single centric, open labelled, prospective study, involving 50 Hyperlipidemic patients of 18 years and older.Data of only Hyperlipidemic patients with Low Density Lipoprotein (LDL -C) ≥ 140 -< 250 mg/dl, High Density Lipoprotein (HDL-C) < 40 -> 60 mg/dl, Total Cholesterol (TC): 200-240 mg/dl and Triglyceride (TG): ≥ 165-< 400 mg/dl and who were prescribed either Atorvastatin 10 mg and Atorvastatin plus Fenofibrate 160 mg were included in the study.Efficacy end points included the change in LDL-C, HDL-C, TC and TG at week 12 and the safety of the treatment was also evaluated based on adverse events.Total of 50 patients were enrolled in the study but 1 patient lost follow up in ATO Group and 2 patients in ATO + FENO Group.Therefore 24 patients in ATO and 23 patients in ATO + FENO group completed study.A statistically significant reduction in LDL-C, TG and TC was seen in both the groups (Atorvastatin 10 mg and Atorvastatin plus Fenofibrate 160 mg).Similarly a statistically significant increase in HDL-C levels was observed in both the groups.ATO + FENO treatment showed a statistically significant reduction in TG at week 12 as compared to ATO alone.Decrease in LDL-C, TC, and TG were 24.86%, 24.81%, and 30.13% respectively and increasing HDL-C 42.37% in ATO + FENO group while the reduction was 21.1%, 21.31%, and 22.84% respectively and increasing HDL-C 38.2% in ATO alone group.The most common adverse events were headache, myalgia and nausea.ATO + FENO treatment showed a greater reduction in lipid parameters as compared to ATO alone (percentage change).Both treatments were well tolerated with similar incidence of adverse events.Study demonstrated that combination treatment was more effective than Atorvastatin alone in reducing LDL-C, Total Cholesterol and Triglyceride.It was also better in increasing HDL-C as compared to Atorvastatin.Statin in combination of fenofibrate may have lesser adverse effects.Thus Combination therapy seems to be a better treatment in patients having Hyperlipidemia.

A field experiment was conducted at the College Agronomy Farm, Department of Agronomy, B. A. College of Agriculture, Anand Agricultural University, Anand, Gujarat during kharif season of the years 2006 and 2007 on loamy sand soil with a view to study the effect of spacing and integrated nutrient management on green cob yield and quality of sweet corn [Zea mays saccharata shut]. Twenty treatment combinations comprising two levels of spacing (45 cm x 20 cm and 60 cm x 20 cm), two levels of FYM (0 t FYM/ha and 10 t FYM/ha) and five fertility levels (100 % RDF, 75 % RDF + Azotobacter, 75 % RDF + Azotobacter + PSB, 50 % RDF + Azotobacter and 50 % RDF + Azotobacter + PSB) were tried under split plot design with four replications. The results revealed that sowing of sweet corn at narrow spacing (45 cm x 30 cm) and application of 10 t FYM ha(-1) with application of 100 % RDF were significantly influence on green cob yield, green fodder yield and get maximum monetary return.

Objective: Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) of oxicam class. According to BCS, Lornoxicam is classified as a low solubility and high permeability drug (class II). Therefore, it often shows dissolution rate-limited oral absorption and high variability in pharmacological effects. The purpose of this study was to prepare pharmaceutical co-crystals of Lornoxicam to enhance solubility and dissolution rate of Lornoxicam. Experimental Work: Co-crystals were prepared by three different methods: liquid assisted grinding, reaction co-crystallization and cooling crystallization by use of four different co-crystal formers which included saccharin, salicylic acid, tartaric acid and pyrogallol. The prepared co-crystals were evaluated for solubility, powder characterization, assay and in vitro dissolution study. The solid state property was characterized by differential scanning calorimetry (DSC), Fourier transfer infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD). Results and Discussion: The solubility and dissolution rate was significantly increased by preparation of co-crystal. Cocrystal prepared by liquid assisted grinding method using saccharin as co-crystal formers (stoichiometric ratio 1:1) and acetonitrile as a drop solvent gave maximum solubility and dissolution rate. The FTIR, DSC and PXRD studies of co-crystals confirmed the formation of co-crystals. Conclusion: From the study carried out it was concluded that stable co-crystals of Lornoxicam with increased solubility and improved in vitro dissolution of Lornoxicam can be successfully prepared. So, co-crystal is a one of the most promising method to improve the solubility and dissolution of drug having poor solubility.