Showing papers by "Kadi Sarva Vishwavidyalaya published in 2014"
TL;DR: Development and evaluation of self-nanoemulsifying drug delivery system (SNEDDS) for improving bioavailability of nelfinavir mesylate (NFV), a protease inhibitor exhibiting pH dependent solubility and variable oral bioavailability is aimed at development and evaluation.
Abstract: The present research was aimed at development and evaluation of self-nanoemulsifying drug delivery system (SNEDDS) for improving bioavailability of nelfinavir mesylate (NFV), a protease inhibitor exhibiting pH dependent solubility and variable oral bioavailability. Maisine 35-1, Cremophor RH-40, and Labrasol were identified as oil, surfactant, and co-surfactant that had best solubility for NFV. Scheffe’s mixture design was used to optimize the amount of components in liquid self-nanoemulsifying drug delivery system (L-SNEDDS) by taking their amounts as independent variable, whereas globule size, drug loading, and percent transmittance were taken as dependent variable. Optimized NFV-L-SNEDDS was then adsorbed on Neusilin US2 to form solid self-nanoemulsifying drug delivery system (S-SNEDDS). NFV loaded L-SNEDDS and S-SNEDDS were characterized for various physicochemical properties, and solid-state properties were determined through differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies. In vitro dissolution using simulated gastric fluid and simulated intestinal fluid, ex vivo drug release study, and in vivo study were performed for pure NFV and NFV-S-SNEDDS. NFV-S-SNEDDS showed more than 90 % drug release in 20 min during drug release studies irrespective of pH of the dissolution medium. In vivo study revealed significant difference between release of NFV from suspension and NFV-L-SNEDDS and NFV-S-SNEDDS when given to rabbits (p < 0.001). NFV-L-SNEDDS and NFV-S-SNEDDS were subjected to stability study as per ICH guidelines, and NFV-S-SNEDDS was found to be stable during the period of study. S-SNEDDS could serve as a potential drug delivery system for NFV.
35 citations
TL;DR: It was concluded that CP loaded MBC possess enhanced skin localization as well as therapeutic activity in vitiligo patients.
21 citations
TL;DR: The anatomy of the human nail,Onychomycosis and its types, onycholysis, and conventional and novel therapies are discussed, as well as design challenges facing optimal drug formulation for ony chomycotic treatment.
Abstract: Onychomycosis is one of the most common nail disorders. It affects 10-30% of the world population and is caused by dermatophytes, non-dermatophytes, molds, and yeasts. Present treatment methods of onychomycosis include oral therapy, topical therapy, and a combination of both; they have mild-to-moderate efficacy, with a relapse and reinfection rate of 20-25%. For oral therapy, newer antifungal compounds (azole class and allylamine class) are being investigated to increase efficacy and minimize side effects. Oral therapy with antifungal agents have severe side effects, with lesser bioavailability and longer duration of treatment. By contrast, topical therapy of onychomycosis is associated with greater patient compliance and fewer systemic side effects and drug interactions. Current topical treatment options of onychomycosis are nail lacquers, ointments, lotions, solutions, and gels, but these formulations have been unsuccessful due to poor penetration and distribution of drugs at the infected site. Therefore, novel therapeutic options are constantly being researched to improve the efficacy of onychomycosis treatment by enhancing the permeation of the drug across the nail to reach the infected site. Various physical and chemical enhancement methods have been studied to increase the permeation of drugs across the nail plate to the nail bed. Device-based therapeutic options have also been investigated to increase the antifungal drug concentration and its effects in the onychomycotic nail. Randomized clinical trials of these novel therapies have demonstrated better efficacy. The present review discusses the anatomy of the human nail, onychomycosis and its types, onycholysis, and conventional and novel therapies. We also review patents granted as well as design challenges facing optimal drug formulation for onychomycosis treatment.
19 citations
TL;DR: The present research work aimed to physicochemically characterize a new generic iron–sucrose preparation (IS-Claris) and establish its equivalency with the reference product (Venofer®) and it was observed that the specifications of IS-claris obtained through these analyses reflect those of Venofer® and hence the two formulations were considered comparable.
Abstract: Intravenous polynuclear iron formulations are vital components in the treatment of iron deficiency anemia associated with chronic kidney disease as well as other diseases associated with gastro-intestinal and cardio-vascular system. Intravenous iron preparations consist of iron-carbohydrate nanoparticles with iron-oxyhydroxide as a core covered by carbohydrate shell. These preparations should be very well characterized in terms of their physicochemical properties and pharmacological profile in order to establish safety and efficacy. The present research work was aimed to physicochemically characterize a new generic iron-sucrose preparation (IS-Claris) and establish its equivalency with the reference product (Venofer®). Various analytical techniques including gel permeation chromatography (GPC), mass spectroscopy (MALDI-TOF), absorption spectroscopy, X-ray diffraction analysis (XRD), nuclear magnetic resonance spectroscopy (proton and (13)C NMR), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were employed. It was observed that the specifications of IS-Claris obtained through these analyses reflect those of Venofer® and hence the two formulations were considered comparable.
19 citations
TL;DR: The method was successfully applied to support a bioequivalence study of 500 mg mycophenolate mofetil tablet in 72 healthy subjects and was validated over a wide concentration range of 15–15000 ng/mL.
17 citations
TL;DR: A selective, sensitive, and robust method for simultaneous determination of three protease inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra performance liquid chromatography-tandem mass spectrometry is described.
Abstract: Objectives. HIV protease inhibitors are used in the treatment of patients suffering from AIDS and they act at the final stage of viral replication by interfering with the HIV protease enzyme. The paper describes a selective, sensitive, and robust method for simultaneous determination of three protease inhibitors atazanavir, darunavir and ritonavir in human plasma by ultra performance liquid chromatography-tandem mass spectrometry. Materials and Methods. The sample pretreatment consisted of solid phase extraction of analytes and their deuterated analogs as internal standards from 50 μL human plasma. Chromatographic separation of analytes was performed on Waters Acquity UPLC C18 (50 × 2.1 mm, 1.7 μm) column under gradient conditions using 10 mM ammonium formate, pH 4.0, and acetonitrile as the mobile phase. Results. The method was established over a concentration range of 5.0–6000 ng/mL for atazanavir, 5.0–5000 ng/mL for darunavir and 1.0–500 ng/mL for ritonavir. Accuracy, precision, matrix effect, recovery, and stability of the analytes were evaluated as per US FDA guidelines. Conclusions. The efficiency of sample preparation, short analysis time, and high selectivity permit simultaneous estimation of these inhibitors. The validated method can be useful in determining plasma concentration of these protease inhibitors for therapeutic drug monitoring and in high throughput clinical studies.
14 citations
TL;DR: A simple, sensitive and high throughput ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed for the determination of tacrolimus in the whole blood of Wistar rats and humans and the reproducibility of the assay was successfully demonstrated.
Abstract: A simple, sensitive and high throughput ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method was developed for the determination of tacrolimus in the whole blood of Wistar rats and humans. Sample preparation involved protein precipitation of the analyte, using sirolimus as the internal standard with ZnSO4 from 50 µL of rat blood/human blood, followed by solid-phase extraction. Chromatographic analysis was conducted on a Waters Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 µm) using 10 mM ammonium acetate (pH 6.0) and methanol (5:95, v/v) under isocratic conditions and detection by MS-MS. Quantitation of the analytes was achieved by multiple reaction monitoring under positive ionization mode. The method was validated over a dynamic concentration range of 0.200-200 ng/mL and had a chromatographic run time of 1.2 min. The extraction recovery for tacrolimus was >96% across three quality control levels. Matrix effect was assessed by the precision (coefficient of variation) values for the calculated slopes of calibration curves from six lots of blood. The method was applied to a pre-clinical study in 25 rats and to a bioequivalence study in 20 healthy Indian subjects. The reproducibility of the assay was successfully demonstrated by the reanalysis of 80 subject samples.
14 citations
TL;DR: In this paper, a simple, sensitive, and specific reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for the quantification of Milnacipran HCl in rabbit plasma.
Abstract: A simple, sensitive, and specific reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for the quantification of Milnacipran HCl in rabbit plasma. Milnacipran HCl and internal standard (IS, Venlafaxine HCl) were extracted by protein precipitation method with chloroform. The separation was performed on a HiQ sil C18 column (250 mm × 4.6 mm i.d., 5 µm). The wavelength was set at 220 nm. The mobile phase was a mixture of potassium dihydrogen phosphate buffer (0.0125 M) and acetonitrile (72:28%, v/v) with 0.20% triethylamine at a flow rate of 1.0 mL/min. The pH of the solution was adjusted to 3.65 with 0.1 M orthophosphoric acid. The calibration curve was linear over the concentration range 0.1–25 µg/mL. The intra-day and inter-day precision was ranged from 3.9 to 7.3% and 5.2 to 10.8%, respectively. Finally, this proposed method was successfully applied to rabbit pharmacokinetics study and yielded the most comprehensive data on systemic exposure of Milnacipran HCl...
12 citations
TL;DR: Clustering of several risk factors at presentation, typically diabetes and hypertension, is common in CAD patients, and utilization of EBM for diabetic and non-diabetic patients is consistent with the recommendations.
Abstract: Objectives: To evaluate and compare clinical and epidemiological characteristics, treatment strategies, and utilization of evidence-based medicine (EBM) among coronary artery disease (CAD) patients with or without diabetes. Materials and Methods: Prospective observational cohort study from a tertiary care hospital in India among patients with CAD (myocardial infarction, unstable angina, or chronic stable angina). Data included demographic information, vital signs, personal particulars, risk factors for CAD, treatment strategies, and discharge medications. We evaluated epidemiologic characteristics and treatment strategies for diabetic and non-diabetic patients. Results: Of 1,073 patients who underwent angiography, 960 patients (30% diabetic) had CAD. Proportion of hypertensive patients was higher among diabetic patients (58 vs 35% non-diabetic, P < 0.001). Similar proportion of patients received medical management in diabetic vs non-diabetic CAD patients (35 vs 34%, P = 0.091); in diabetics the use of surgical procedure was higher (22 vs 17%, P = 0.0230) than interventional strategy (percutaneous transluminal coronary angioplasty, 43 vs 49%, P = 0.0445). Key medications (antiplatelet agents, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), beta-blockers, and ahtihyperlipidemic agents) were prescribed in 95, 53/12, 67, and 91% diabetic (n = 252) and 96, 51/8, 67, and 94% non-diabetic (n = 673) patients, respectively on discharge. Conclusions: Clustering of several risk factors at presentation, typically diabetes and hypertension, is common in CAD patients. Though diabetic patients are managed more conservatively, utilization of EBM for diabetic and non-diabetic patients is consistent with the recommendations.
9 citations
TL;DR: The poorer HRQOL as assessed by the EQ-5D questionnaire among patients with CAD who had diabetes highlights the need of individualized treatment programs to improve outcomes in this most vulnerable population.
Abstract: Objective To assess the influence of diabetes on health-related quality of life (HRQOL) in patients with coronary artery disease (CAD) and identify predictors of health status at 1-year follow-up after an acute coronary event. Methods A prospective cohort study in patients diagnosed with CAD at a tertiary care hospital from India. The EuroQol five-dimensional (EQ-5D) questionnaire was administered at 1-year follow-up. Multivariate stepwise liner regression was used to assess predictors of EQ visual analogue scale (VAS) and EQ-5D questionnaire utility scores. Respondents reporting problems on the EQ-5D questionnaire were stratified by the presence of diabetes at baseline for comparison. Results Of 960 (30% diabetic) patients with CAD enrolled in a main study cohort, 306 (76% males, 21% diabetic) responded to the HRQOL questionnaire at 1 year. Diabetic patients reported more difficulties/problems than did nondiabetic patients for EQ-5D questionnaire dimensions (mobility, 12.3% vs. 4.1%, P = 0.03; usual activities, 56.9% vs. 41.3%, P = 0.03; pain/discomfort, 50.8% vs. 17.8%, P 0.001; anxiety/depression, 33.8% vs. 14.9%, P 0.001), except for self-care (12.3% vs. 17.5%, P = 0.35). Mean ± SD EQ VAS and EQ-5D questionnaire utility scores were significantly lower for patients with CAD with diabetes versus those without diabetes (0.75 ± 0.15 vs. 0.83 ± 0.15, P = 0.0002, and 67.8 ± 8.8 vs. 73.6 ± 5.4, P = 0.0001, respectively). Presence of diabetes, use of beta-blockers on discharge, and treatment strategy significantly influenced the VAS score, whereas myocardial infarction as final diagnosis and the presence of prior CHF predicted worse EQ-5D questionnaire utility scores. Conclusions The poorer HRQOL as assessed by the EQ-5D questionnaire among patients with CAD who had diabetes highlights the need of individualized treatment programs to improve outcomes in this most vulnerable population.
8 citations
TL;DR: The study showed that Z-spray ion source provided minimum interference from phospholipids compared with other ion source designs, and provided better and efficient transfer of gas phase ions into the mass analyzer compared with angular and orthogonal spray.
Abstract: Background: This study evaluates the performance of three electrospray ionization source designs to monitor the interference of plasma phospholipids for reliable estimation of rivastigmine by LC–MS/MS for method ruggedness. The variation in the area response due to matrix effects was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. Results: The observed interference due to coeluting phospholipids (m/z: 524.0/184.0) at the retention time of rivastigmine was 39.5, 12.9 and 0.4% using angular spray, orthogonal spray and dual orthogonal ion source spray design, respectively. Similarly, %CV for standard line slopes was 6.9, 4.6 and 2.0, respectively. Conclusion: Z-spray source design provided better and efficient transfer of gas phase ions into the mass analyzer compared with angular and orthogonal spray. The study showed that Z-spray ion source provided minimum interference from phospholipids compared with other ion source designs.
01 Dec 2014
TL;DR: This paper proposes extended API specifications that can help in dynamic configuration of the middleware for execution of applications and efficient utilization of resources.
Abstract: In this fast and rapidly developing IT era, Grid computing is emerging and is being used in many industries and organizations. This has opened a window of attraction for research on Grid Architecture, Middleware and Services.
Goddard Space Flight Center1, The Catholic University of America2, Ariès3, Indian Institute of Technology (BHU) Varanasi4, Kyung Hee University5, Kumaun University6, Tata Institute of Fundamental Research7, Kadi Sarva Vishwavidyalaya8, Physical Research Laboratory9, California State University, Northridge10
TL;DR: In this paper, the authors considered homologous C6.6 and C9.4 coronal mass ejections (CMEs) during the disk passage of NOAA 11158.
TL;DR: In this paper, a solid dispersion (SD) based sustained release system of Milnacipran HCl (MH) was developed using solvent evaporation technique and different waxes at ratio of 1: 1, 1:1.5 and 1.75 with drug were developed by melting method.
Abstract: In present day, availability of various carriers, innovative techniques of production and plenty of solvents support the growth of solid dispersion (SD) technology in pharmaceutical industries to overcome many issues. The present study was aimed to develop SD based sustained release system of Milnacipran HCl (MH). The SD containing ethyl cellulose, Eudragit RLPO and Eudragit RSPO at drug–polymer ratios of 1:1, 1:2, and 1:3 were developed using solvent evaporation technique and different waxes at ratio of 1:1, 1:1.25, 1:1.5 and 1:1.75 with drug were developed by melting method. The physicochemical properties of SD were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The desired SD batch was further compressed into tablet unit to achieve predetermined once a day drug release. Tablets prepared were evaluated for physicochemical parameters, in vitro drug release, drug release kinetics and scanning electron microscopy. Out of selected carriers, bees wax had shown maximum release retardation. The results of FTIR, DSC and XRD studies exhibited poor interaction amongst MH–bees wax and retention of crystalline state of MH in SD system. The presence of Benecel® (HPMC K 200 M; 75 mg) in tablets comprising SD (1:1.25, MH:bees wax) revealed remarkable drug release extension and it was considered an optimal. The later was submitted to short term stability study and its results indicated the stable characteristic of system. Drug release from optimized formulation fitted well into Higuchi model with anomalous diffusion. The compressed unit of SD system of highly water soluble drug can be successful single day regimen.
TL;DR: The bioassay results revealed that the majority of the N -benzothiazole-substituted piperazine derivatives exhibited moderate to good bioefficacies with encouraging MICs.
Abstract: Eleven N-phenyl- and 11 N-benzothiazolyl-2-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)acetamides have been synthesised by a simple and efficient method. The 22 novel compounds were tested for their ...
TL;DR: The optimized solid-phase extraction provided cleaner extracts with reduced matrix effect from plasma phospholipids compared with protein precipitation and liquid-liquid extraction.
Abstract: Background: The objective of the present work was to minimize or eliminate the matrix effect due to plasma phospholipids as observed during sample preparation for accurate determination of dronedarone and its active metabolite, desbutyldronedarone by LC–ESI-MS/MS. Results: The extraction recovery and matrix factors ranged from 93.27 to 95.14% and 0.99 to 1.02, respectively, for both the analytes. A linear concentration range of 0.10 to 150 ng/ml was established for both the analytes. The analytes were efficiently resolved (Rs 2.37) on Kromasil® (AkzoNobel, Bohus, Sweden) C18 column within 3.0 min. The assay reproducibility was determined by reanalysis of 72 incurred samples with % change within ±10%. Conclusion: The optimized solid-phase extraction provided cleaner extracts with reduced matrix effect from plasma phospholipids compared with protein precipitation and liquid–liquid extraction.
TL;DR: This data indicates that HLA class II is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain and that a sequence of amino acids, termed the shared epitope, are involved in the disease process.
Abstract: Background Genetic predisposition to rheumatoid arthritis related to the presence of specific polymorphic HLA sequences has been frequently reported [1,2]. HLA class II is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Association studies have provided evidence that a sequence of amino acids, termed the shared epitope, are involved in the disease process [3].