Development and validation of UV Spectrophotometric method for simultaneous estimation of Efonidipine hydrochloride ethanolate and Chlorthalidone in their synthetic mixture

Efonidipine Hydrochloride Ethanolate and Chlorthalidone is used in management of hypertension and under clinical phase 3 study. The development of quality control method is required for accurate analysis of both drugs. Two simple, precise and economical UV spectrophotometric methods have been developed for the simultaneous estimation of Efonidipine Hydrochloride Ethanolate and Chlorthalidone in their synthetic mixture. Method I is simultaneous equation method (Vierodt’s Method), which is based on measurement of absorption at 251 and 227 nm i.e. λmax of Efonidipine Hydrochloride Ethanolate and Chlorthalidone, respectively. Method II is first order derivative was based on the measurement of absorbance of Efonidipine Hydrochloride Ethanolate measure at 283.2 nm (ZCP of Chlorthalidone) and absorbance of Chlorthalidone measure at 250.8 nm (ZCP of Efonidipine Hydrochloride Ethanolate). Linearity was observed in the concentration range of 6.4-38.4 µg.mL-1 for Efonidipine hydrochloride ethanolate and 2-12 µg.mL-1  for Chlorthalidone using methanol as a solvent. The accuracy of methods was assessed by recovery studies and was found to be within range of 98-102% for both the drugs. Precision of the methods was estimated by repeatability and intermediate precision studies. The % RSD values were found to be less than 2, proving methods were precise. Two methods were compared using F- test. The results were validated statistically as per ICH Q2 R1 guideline and were found to be satisfactory

APTAMERS: A NOVEL APPROACH FOR BIO-IMAGING, BIO-SENSING AND TARGETED DRUG DELIVERY SYSTEMS

This review describes recent progress made in the aptamer and application of biomedically relevant aptamers and relates them to their future clinical prospects.Aptamers are single-stranded nucleic acid or amino acid polymers that recognize and bind to targets with high affinity and selectivity. In nature they exist as a nucleic acid based genetic regulatory element called a riboswitch. Aptamers, simply described as chemical antibodies, are synthetic oligonucleotide ligands or peptides that can be isolated in vitro against diverse targets including toxins, bacterial and viral proteins, virus-infected cells, cancer cells and whole pathogenic microorganisms. They are isolated by the technique called SELEX- systematic evolution of ligands by exponential enrichment. The applications of aptamers range from diagnostics and biosensing, target validation, targeted drug delivery, therapeutics, templates for rational drug design to biochemical screening of small molecule leads compounds, in virology,as novel radio pharmaceuticals.Â

simultaneous determination of metronidazole and miconazole nitrate in gel by

ABSTRACT A new, simple, precise, rapid and selective high-performance thin-layer chromatographic (HPTLC) method for the simultaneous quantification of Metronidazole (MTZ) and Miconazole nitrate (MCZ) in gel has been developed. It was performed on silica gel 60 GF 254 Thin Layer Chromatographic plates using mobile phase comprising of Toluene: Chloroform: Methanol (3.0:2.0:0.6 v/v) and the detection was carried out at 240 nm using densitometer. The retention factors of MTZ and MCZ were 0.34 and 0.55 respectively. Calibration curves were linear in the range of 300-700 ng/spot of MTZ and 600-1400 ng/spot of MCZ both by height and by area. The percent recovery of the drugs from gel carried out by standard addition method was found to be 100.13±1.59 (by height) and 98.92±0.76 (by area) for MTZ and 99.49±1.58 (by height) and 99.63±1.46 (by area) for MCZ indicative of accuracy and precision of simultaneous determination of MTZ and MCZ nitrate

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Development and validation of UV Spectrophotometric method for simultaneous estimation of Efonidipine hydrochloride ethanolate and Chlorthalidone in their synthetic mixture

Efonidipine Hydrochloride Ethanolate and Chlorthalidone is used in management of hypertension and under clinical phase 3 study. The development of quality control method is required for accurate analysis of both drugs. Two simple, precise and economical UV spectrophotometric methods have been developed for the simultaneous estimation of Efonidipine Hydrochloride Ethanolate and Chlorthalidone in their synthetic mixture. Method I is simultaneous equation method (Vierodt’s Method), which is based on measurement of absorption at 251 and 227 nm i.e. λmax of Efonidipine Hydrochloride Ethanolate and Chlorthalidone, respectively. Method II is first order derivative was based on the measurement of absorbance of Efonidipine Hydrochloride Ethanolate measure at 283.2 nm (ZCP of Chlorthalidone) and absorbance of Chlorthalidone measure at 250.8 nm (ZCP of Efonidipine Hydrochloride Ethanolate). Linearity was observed in the concentration range of 6.4-38.4 µg.mL-1 for Efonidipine hydrochloride ethanolate and 2-12 µg.mL-1  for Chlorthalidone using methanol as a solvent. The accuracy of methods was assessed by recovery studies and was found to be within range of 98-102% for both the drugs. Precision of the methods was estimated by repeatability and intermediate precision studies. The % RSD values were found to be less than 2, proving methods were precise. Two methods were compared using F- test. The results were validated statistically as per ICH Q2 R1 guideline and were found to be satisfactory

Insights of potential G-quadruplex sequences in telomeres and proto-oncogenes

Guanine rich sequences have the ability to fold into stable 4 stranded structures called G-quadruplex under physiological concentrations of Na+ or K+. G-quadruplexes are found in telomeres, being stable structures under the control of telomerase binding proteins. They are also identified throughout the genome and are enriched in promoter regions of protein coding genes, upstream and downstream of the transcription initiation sites. A number of these promoter quadruplexes have been investigated for several proto-oncogenes. The formation of these quadruplexes can lead to chemical intervention of gene expression using a G-quadruplex binding ligand. We review location, configuration, and stabilization of these quadruplexes in some of the important promoters with regards to their potential as anticancer target.</jats:p