INFLUENCE OF HYDROXYPROPYL-β-CYCLODEXTRIN ON REPAGLINIDE RELEASE FROM SUSTAINED RELEASE BIOADHESIVE BUCCAL TABLETS

Objective: The purpose of this investigation was to study the influence of cyclodextrin complexation on development of sustained release bio-adhesive repaglinide tablets for buccal delivery. Methods: Based on preliminary phase solubility studies, solid complexes prepared by freeze-drying method in 1:1 molar ratio were selected and characterized by Fourier transform infrared spectroscopy to corroborate the fact of complex formation. The sustained release repaglinide tablets were produced by direct compression and this drug or complexed –loaded hydrophilic matrices using HPMC, Sodium CMC and Carbopol as muco-adhesive polymers were assessed for in vitro bioadhesion strength, in vitro release modulation, surface pH, % moisture absorption and ex vivo permeation through porcine buccal membrane. Results: When the drug was incorporated as repaglinide-Hydroxypropyl-β-Cyclodextrin (HP-β-CD) freeze-dried product, total amount of drug permeated from the tablet through epithelium in about 12 hrs, displaying a constant release regimen after a transient period. The effect of HP-β-CD incorporation on the release mechanism was rationalized on the basis of the interplay of different physical phenomena: erosion and swelling of the tablet, drug dissolution, and complex formation. Formulation F10 showed % moisture absorption of 23.46 for 4hrs, surface pH 6.9±0.015, Peak detachment force 3.65±0.18 N, Work of adhesion 1.12±0.10 mJ, and in vitro drug release 98.31% in 6h. The feasibility of buccal administration of repaglinide was assessed by permeation experiments on excised mucosa of pig. The ex vivo permeation studies demonstrated that the matrix tablets containing repaglinide–HP-β-CD (F10) solid complex exhibited significantly higher drug permeation (92.18 % for 12hrs) compared to all of the other formulations tested, which could be attributed to both, the presence of the polymers, and the drug-cyclodextrin complexation. The flux was found to be increased by 1.12-1.37 folds with a permeability coefficient of 0.017-0.018. Conclusion: The results demonstrate that the formulations with inclusion complexes afford high utility as a trans-mucosal drug delivery system for improved drug release and permeability.   KEY WORDS: Repaglinide, Freeze drying, HP-β-CD complexation, Bioadhesion, Ex-vivo permeation, Solubility &nbsp

Greener One-pot Synthesis of Chromeno Oxazin and Oxazin Quinoline Derivatives and their Antibacterial Activity

An efficient green method for the synthesis of oxazino quinoline-2-amine derivatives, oxazino quinoline derivatives and chromeno oxazin-5-one derivatives have been synthesized through cyclization of aromatic aldehyde, ammonium acetate, substituted amides and 8-hydroxy-quinoline or 4-hydroxy coumarin by one-pot condensation method is described. The synthesized compounds are characterized by FT-IR, 1H NMR and MASS spectral techniques and are screened further for biological activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis using cup plate method and disc diffusion method

Measurement of 92Mo(n,α)89Zr and 97Mo(n,p)97Nb reactions at the neutron energy 13.52 MeV with covariance analysis

218-222The cross sections have been estimated for the Nuclear reactions 92Mo(n,α)89Zr and 97Mo(n,p)97Nb produced in Purnima neutron generator at neutron energy of 13.52±0.0045 MeV using activation analysis and off-line γ -ray spectrometric techniques. 27Al(n,α)24Na has been used as a monitor reaction. The covariance analysis for these cross sections has been carried out by taking into consideration of partial uncertainties of different attributes and correlations between the attributes. The cross section values of the present study have been compared with EXFOR, ENDF data of various libraries and theoretical data of TALYS-1.8 code

Microstructural evolution under low shear rates during Rheo processing of LM25 alloy

© ASM InternationalMicrostructural features of LM25 alloy processed by two different routes: (1) conventional casting, and(2)shear casting based on inclined heated surface are studied. The microstructures of the primary phase for the shear-cast samples show rosette or ellipsoidal morphologies. Heat transfer of contacting melt with the inclined tube surface and shear stress exerted on the layers of the melt as result of gravitational force are crucial parameters for the microstructural evolution. Compared to those produced by conventional casting, shear-cast samples have a much improved tensile strength and ductility due to globular microstructure

Performance of blackgram genotypes under moisture deficit stress -Variability in physiological and yield contributing attributes

Abstract Water deficit stress is the most important abiotic stresses which affects the physiological parameters and crop yield. Blackgram (Vigna mungo L. Hepper) is one of the highly prized pluses in India and second most important pulse crop. A field experiment was conducted with seventeen blackgram genotypes during 2014 to assess the impact of water deficit stress on physiological parameters such as Anet, gs, Tr, WUE, SPAD chlorophyll meter reading (SCMR) and yield parameters (i.e.) pod number, seed number, pod weight and seed yield. Imposing water deficit stress at flowering stage, the reduction of physiological and yield parameters were observed. The results indicated that a wide diversity among the genotypes in their physiological and yield related parameters under both moisture levels. The genotype IC398971 was found to be physiologically efficient even with water deficit stress and also recorded moderate seed yield. While the genotype PU-19 with moderate physiological values registered highest seed yield under both well watered and water deficit stress conditions. Among the selected germplasm these two genotypes are having tolerant to water deficit stress with better stability of physiological and yield parameters

Whole genome sequence analysis of blood lipid levels in \u3e66,000 individuals

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids

Experimental and computational studies of sonochemical assisted anchoring of carbon quantum dots on reduced graphene oxide sheets towards the photocatalytic activity

Herein, carbon quantum dots (CQDs) are anchored on reduced graphene oxide (rGO) sheets by sonochemical assisted method. The developed carbon quantum dots/reduced graphene oxide (CQDs/rGO) catalyst shows enhancement in the photocatalytic degradation of methylene blue and methyl orange under visible light compared to that of individual CQDs and rGO components. The improved performance of the CQDs/rGO catalyst has been attributed to efficient separation of photogenerated charge carriers as studied by photoluminescence studies and to increase in the surface area as studied by Brunauer-Emmett-Teller method. The photocatalytic degradation is studied in detail by varying catalyst loading, dye concentration and the rate constant is determined by first order kinetics. The enhancement in photocatalytic activity of CQDs/rGO catalyst is validated by first principles density functional theory (DFT) calculations which shows the enrichment in density of states thereby decreasing the work function

Morphological and biochemical factors associated with resistance to Maruca vitrata (Geyer) (Lepidoptera: Pyralidae) in short duration pigeonpea

The spotted pod borer Maruca vitrata (Geyer) is known for its economic importance throughout its geographical distribution because of its destructive nature to reproductive parts of several grain legume crops including pigeonpea. In view of the importance of the pest, the present study was carried out on the association of different morpho-chemical traits with resistance/susceptibility to M. vitrata at the International Crops Research Institute for the Semi-Arid Tropics, Patancheru, India. Trichome length and density, sugars, proteins and phenols were found to be associated with resistance to M. vitrata in short-duration pigeonpea genotypes. Pod damage by M. vitrata on different short-duration pigeonpea genotypes in the field ranged from 5.8 to 68%. Laboratory studies showed less consumption of food and reduced larval and pupal weights of M. vitrata when reared on the resistant genotypes ICPL 98003 and ICPL 98008 indicating antibiosis effects of the genotypes. Trichome density on upper and lower surfaces of the leaf (390 and 452/9 mm2), and length (3.5 mm) and trichome density (442/9 mm2) and length (5.9 mm) on pods were found positively correlated with the resistant genotype ICPL 98003. High sugar content in flowers (22%) and pods (10.6%) was responsible for the susceptibility of ICPL 88034, while high phenol concentration in flowers (6.5%) and pods (9.3%) in ICPL 98003 was responsible for resistance. Protein content in pods was significantly higher (25.5%) in susceptible ICPL 88034 when compared with resistant ICPL 98003 (16.5%). Based on these results, ICPL 98003 and ICPL 98008 were categorized as highly resistant and ICPL 98012 as moderately resistant. This paper discusses the physico-chemical traits associated with resistance to M. vitrata in short-duration pigeonpea genotypes

Ethanol production from xylose by pichia stipitis NRRL Y-7124 in a stirred tank bioreactor

The ethanol production by Pichia stipitis was evaluated in a stirred tank bioreactor using semidefined medium containing xylose (90.0 g/l) as the main carbon source. Experimental assays were performed according to a 22 full factorial design to evaluate the influence of aeration (0.25 to 0.75 vvm) and agitation (150 to 250 rpm) conditions on ethanol production. In the studied range of values, the agitation increase and aeration decrease favored ethanol production, which was maximum (26.7 g/l) using 250 rpm and 0.25 vvm, conditions that gave a volumetric oxygen transfer coefficient (kLa value) of 4.9 h-1. Under these conditions, the ethanol yield factor, ethanol productivity, and the process efficiency were 0.32 g/g, 0.32 g/l.h, and 63%, respectively. These results are promising and contribute to the development of a suitable process for ethanol production from xylose by Pichia stipitis.The authors gratefully acknowledge Santander, Fapesp, Capes, and CNPq (Brazil)

Critical assessment of infants born to mothers with drug resistant tuberculosis

Background: There have been no detailed descriptions of infants born to mothers treated for drug resistant TB in pregnancy. Critical case history assessment is important to identify risks and guide clinical practice. Methods: In a cohort of pregnant women with multidrug or rifampicin resistant (MDR/RR)-TB enrolled between 1 January 2013 and 31 December 2022, we followed mother-infant pairs until the infant was 12 months old. We performed critical case history assessments to explore potential mechanisms of Mycobacterium tuberculosis transmission to the infant, and to describe the clinical presentation and disease trajectories observed in infants diagnosed with TB. Findings: Among 101 mother-infant pairs, 23 (23%) included infants diagnosed with TB disease; 16 were clinically diagnosed and seven had microbiological confirmation (five MDR/RR-TB, two drug-susceptible TB). A positive maternal sputum culture at the time of delivery was significantly associated with infant TB risk (p = 0.023). Of the 12 infants diagnosed with TB in the first three months of life, seven (58%) of the mothers were culture positive at delivery; of whom four reported poor TB treatment adherence. However, health system failures, including failing to diagnose and treat maternal MDR/RR-TB, inadequate screening of newborns at birth, not providing appropriate TB preventive therapy (TPT), and M. tuberculosis transmission from non-maternal sources also contributed to TB development in infants. Interpretation: Infants born to mothers with MDR/RR-TB are at greatest risk if maternal adherence to MDR/RR-TB treatment or antiretroviral therapy (ART) is sub-optimal. In a high TB incidence setting, infants are also at risk of non-maternal household and community transmission. Ensuring maternal TB diagnosis and appropriate treatment, together with adequate TB screening and prevention in all babies born to mothers or households with TB will minimise the risk of infant TB disease development. Funding: South African Medical Research Council