QUALITY CONTROL ASSAY OF TWO ANTIHYPERTENSIVE REPRESENTATIVES USING RP-HPLC BASED METHODOLOGY: STRESS ASSESSMENT ON ANTIHYPERTENSIVE REPRESENTATIVES

Objective: A quick simultaneous separation and quality control assay of two antihypertensive representatives, Azilsartan (AZIL) and Cilnidipine (CLIN) in bulk and tablet formulation was developed and validated using a Reverse phase (RP) HPLC method within a run time of 10 min. Methods: All chromatographic separations of AZIL and CILN were operated on a “Supelco C18 column (250 × 4.6 mm, 5 μ)”, using a mobile phase of Na2SO4 (0.1 M, pH 4.0): methanol at 60:40 (v: v) ratio and the samples were analyzed at 239 nm. Stability assessments of AZIL and CILN were carried out as per the ICH Q1A (R2) regulation. The methodology for determining AZIL and CILN in bulk and formulations tablets was verified by adhering to International Conference on Harmonization (ICH) recommendations. Results: Retention times of AZIL and CILN samples were 4.023 and 5.732 min, respectively, indicating a quick elution time. Over the tested range of 20–60 µg/ml for AZIL and 5–15 µg/ml for CILN determination, calibration curves have displayed linearity and satisfactory results. LOD of AZIL and CILN are 0.083 µg/ml and 0.056 µg/ml, respectively. The approach suggested herein has satisfactory precision (RSD: 0.1013% for AZIL and 0.4944% for CILN) and accuracy (recovery: 99.20 to 100.34 % for AZIL and 100.17 to 101.59 % for CILN). Furthermore, the approach has also been shown to be effective in detecting degradants of AZIL and CILN and resolving them with high resolution. Conclusion: This approach is shown to be acceptable for the accurate quality control assay of two antihypertensive representatives, AZIL and CLIN in both bulk and tablet formulation

MIXED SCALING APPROACH TO ESTABLISH BIOEQUIVALENCE OF LANSOPRAZOLE DELAYED RELEASE CAPSULE IN FASTING SPRINKLE WITH APPLE SAUCE STUDY IN HEALTHY SUBJECTS

Objective: The aim of the present study was to establish bioequivalence of highly variable generic lansoprazole (LSP) delayed release (DR) capsule,exploring minimal number of healthy volunteers by mixed scaling approach as oppose to average bioequivalence approach.Methods: This was an open-labeled, three-treatment, three-periods, three-sequences, single-dose, partial replicate crossover trial conducted in 36 +4 (stand by) healthy adult human subject in Indian origin.Results: Non-parametric Wilcoxon sign rank test at 95% confidence interval failed to conclude significance difference in T and t1/2 between theformulations. The intra subject standard deviation of the reference formulation was 0.340 for C, 0.249 for area under curve up to last measurabletime point (AUCT) and 0.244 for area under curve up to infinity time (AUCI) parameters. The reference scaling as proposed by Haider et al., 2008, wasapplied for Cmax, maxand constant scaling was applied for AUCT and AUCI metrics. No significance difference between two formulations were observedwhen data were analyzed by Analysis of Variance (p<0.05). Westlake 90% confidence limit, as well as two one-sided t-test as proposed by Schurimanand the Anderson-Hauck power analysis all fell under the predefine bioequivalence criteria for mixed scaling.Conclusion: The generic LSP DR capsules were found to bioequivalent with reference drug under fasting study with apple sauce with respect to rateand extent of absorption. The mixed scaling statistical analysis approach used to establish bioequivalence with a minimum number of subjects wasfound reliable and utilize 40 subjects as opposed to 110 subjects need to establish bioequivalence in traditional average bioequivalence approach.Keywords: Mixed scaling, Techniques, Non-parametric, Bioequivalence, Delayed release

Zinc Oxide Nanoparticles Catalyzed Condensation Reaction of Isocoumarins and 1,7-Heptadiamine in the Formation of Bis-Isoquinolinones

The diversified bis-isoquinolinones were obtained in two steps, utilizing homophthalic acid and various acid chlorides providing 3-substituted isocoumarins in the first step which on further condensation with 1,7-heptadiamine involving C–N bond formation from the lactone in the presence of 10 mol% zinc oxide nanoparticles (ZnO NPs) (<150 nm) afforded the desired bis-isoquinolinones in high yield and purity. The synthesized compounds were then characterized using FTIR, 1H NMR, 13C NMR, and HRMS techniques

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p-Pb collisions

Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at root s = 13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (p(T)) of 0.2 GeV/c and up to p(T) = 35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p-Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the p(T) range 0.5 < p(T) < 26 GeV/c at root s(NN) = 8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p-Pb collisions grow faster than linear with the self-normalised multiplicity. A strong p(T) dependence is observed in pp collisions, where the yield of high-p(T) electrons increases faster as a function of multiplicity than the one of low-p(T) electrons. The measurement in p-Pb collisions shows no p(T) dependence within uncertainties. The self-normalised yields in pp and p-Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

Formulation and Evaluation of Bupivacaine-Loaded Glutaraldehyde-Crosslinked High Molecular Weight Chitosan Microspheres

Purpose: To develop a chitosan microsphere carrier system of bupivacaine for buccal administration. Methods: Chitosan microspheres loaded with bupivacaine were prepared by emulsification technique based on glutaraldehyde cross-linking and drug-loaded chitosan microsphere were coated with polyglycolic acid (PGA) film The formulated microspheres were characterized by x-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and in vitro release was performed in pH 7.4 phosphate buffer both in the presence and in absence of lysozyme. Results: Encapsulation yield was 83.1 %. SEM studies indicate that the microspheres were spherical and had a relatively smooth surface. XRD and DSC data indicate that there was no interaction between the drug and polymer. In vitro results show that in the presence of lysozyme, 39 % of the drug was released from the microspheres after 4.5 days while maximum drug release (42.5 %) was achieved on day 11. This compares with 31 % drug release on 4.5th day and 38 % on 11th day; maximum drug release occurred on day 11 in the absence of lysozyme. Conclusion: It is evident from this study that microspheres can potentially be used for controlled release of of bupivacaine for the management of dental pain in the buccal cavity

Simultaneous Spectrophotometric Determination of Valsartan and Ezetimibe in Pharmaceuticals

Purpose: To develop a direct, simple and extraction-free spectrophotometric method for the simultaneous estimation of valsartan and ezetimibe in pharmaceuticals. Methods: A spectrophotometric method for the determination of valsartan and ezetimibe was developed using acidic dyes, namely, bromophenol blue (BPB) and bromocresol green (BCG). The method was based on selective ion-pair formation between valsartan and the acidic dye. The yellow coloured ion-pair induces a bathochromic shift in the spectrum with maximum absorbance at 425 and 428 nm for BPB and BCG, respectively. The developed method was validated as per ICH guidelines. Results:With BPB, the ion-pair formed obeyed Beer`s law in the ranges 5 - 40 and 1 - 50 μg/mL for valsartan and ezetimibe, respectively. The assay data for valsartan and ezetimibe were, 99.39 ± 0.53 and 98.17 ± 0.91 %, respectively, for the commercial formulation, and 99.41 ± 0.48 and 98.16± 0.89 %, respectively, for the developed formulation. The method was validated and the correlation coefficient for valsartan and ezetimibe were 0.995 and 0.999, respectively. Recovery was in the range 99.3 - 100.3 %. Conclusion: The proposed method is reproducible, accurate, robust and suitable for the simultaneous quantitative analysis of the studied drugs in bulk and dosage formulation

Simultaneous Quantitation of Lead and Cadmium on an EDTA-Reduced Graphene Oxide-Modified Glassy Carbon Electrode

Cadmium (Cd) and lead (Pb) are classified as category one toxicants. The provisional guideline values, according to the World Health Organization (WHO), for Cd and Pb are 3 and 10 ppb, respectively. An easy, quick, and cheap analytical technique is in demand for the determination of these toxic heavy metals in water. Hence, a novel electrochemical sensing platform is developed by modifying the glassy carbon electrode with ethylenediaminetetraacetic acid (EDTA)-functionalized reduced graphene oxide (ErGO) for the low-cost simultaneous quantitation of toxic heavy-metal ions, lead and cadmium, in real water samples. EDTA is grafted to the surface of graphene oxide, via amine linkage, and the oxygen functionality is reduced by a green agent, tyrosine. Various physical and electrochemical characterizations of the as-prepared electrocatalytic material were performed by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), ζ-potential, ultraviolet diffuse reflectance spectroscopy (UV-DRS), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), etc. The glassy carbon electrode (GCE) is modified with ErGO by a simple drop-casting method for simultaneous metal-ion quantitation by differential pulse voltammetry (DPV). EDTA functionalization of graphene oxide and its further reduction using the green agent enhance the stability and sensitivity of the electrode substrate. The limits of detection for cadmium and lead ions calculated for ErGO/GCE are 1.02 and 2.52 ppb, while the limits of quantification for lead and cadmium ions are 3.41 and 8.4 ppb, and their sensitivities are 0.8 and 0.6 nA/ppb, respectively. Real river water contains 200.2 ± 0.38 ppb of Pb2+ ions (mean ± stdev, n = 3) by the DPV technique, which is validated by ICP-OES analysis