Development of two charge transfer complex spectrophotometric methods for determination of tofisopam in tablet dosage form

Purpose: To develop a simple, fast and sensitive spectrophotometric method for the determination of tofisopam in tablet dosage form. Methods: Tofisopam as n-electron donor was reacted with two π-acceptors, namely, chloranilic acid (ChA), and 7,7,8,8 tetracyanoquinodimethane (TCNQ) to form charge transfer complexes. The complexes were evaluated spectrophotometrically at 520 and 824 nm for ChA and TCNQ, respectively. The optimum conditions for the reaction were determined and optimized. The developed method was compared with Japanese Pharmacopeia method. Results: The calibration curve was linear in the ranges 25 – 125 and 30 – 150 μg/mL for ChA and TCNQ, respectively. The lower limit of detection was 8.0 and 10.0 μg/mL for ChA and TCNQ, respectively while the slope and intercept of the calibration curves were 0.0025 and 0.011 and 0.0115 and -0.237, for ChA and TCNQ, respectively. Conclusion: The developed methods for tofisopam have good accuracy and precision, and comparable to a standard pharmacopeial method. The methods can be applied for routine analysis and in quality control.

In vitro technique for selecting onion FOR white rot disease- resistance

In vitro selection is one of the most effective and efficient techniques for plant improvement. This is due to its ability to isolate plants with the desired character(s), either by applying a selection agent on the culture media to drive the selection of somaclones with the required character(s), or by establishing particular conditions that change in the genomes of somaclones toward the required character. The objective of this study was to identify a suitable protocol for in vitro selection of Allium white rot disease ( Sclerotium cepivorum ) tolerance in commercial Egyptian onion varieties, namely Giza 20, Giza 6 and Beheri Red. Oxalic acid (OA), the phytotoxin produced by Sclerotium cepivorum, was used as the selective agent. Seeds of the three Egyptian varieties were germinated on four concentrations (0.0, 0.02, 0.2, 2 and 20 mM) of Oxalic acid. Among the tested cultivars, Beheri Red had the highest germination frequency (52%) at all concentrations tested, followed by Giza 20 (42.6%), and Giza 6 at (32%). Cotyledon explants from the varieties were cultured on toxic MSBDK medium, supplemented with 0, 3, 6 and 12 mM OA. The survival of calli on MSBDK free toxic medium was 70.7% for all tested cultivars; however, MSBDK-stressed medium, with 3 mM OA reduced the viable calli to 42.1%. The highest OA concentration (12 mM) completely inhibited calli induction from cotyledons explants. A medium supplement with 3 mM OA retarded 80% of calli growth. Among 156 tested calli of Beheri Red, only 23 calli (14.7%) survived on toxic medium for 45 days. Similarly, there was 15.6% survival for Giza 20 calli, while 40.1% of the Giza 6 calli survived. Plantlets were regenerated from surviving calli and transplanted onto ex vitro, and formed bulb after acclimatisation.

Cynomolgus monkeys ( Macaca fascicularis ) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design

Purpose: To develop and optimise some variables that influence fluoxetine orally disintegrating tablets (ODTs) formulation. Methods: Fluoxetine ODTs tablets were prepared using direct compression method. Three-factor, 3- level Box-Behnken design was used to optimize and develop fluoxetine ODT formulation. The design suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and compression force (X3) and then their effect was monitored on tablet weight (Y1), thickness (Y2), hardness (Y3), % friability (Y4), and disintegration time (Y5). Results: All powder blends showed acceptable flow properties, ranging from good to excellent. The disintegration time (Y5) was affected directly by lubricant concentration (X1). Lubricant mixing time (X2) had a direct effect on tablet thickness (Y2) and hardness (Y3), while compression force (X3) had a direct impact on tablet hardness (Y3), % friability (Y4) and disintegration time (Y5). Accordingly, Box-Behnken design suggested an optimized formula of 0.86 mg (X1), 15.3 min (X2), and 10.6 KN (X3). Finally, the prediction error percentage responses of Y1, Y2, Y3, Y4, and Y5 were 0.31, 0.52, 2.13, 3.92 and 3.75 %, respectively. Formula 4 and 8 achieved 90 % of drug release within the first 5 min of dissolution test. Conclusion: Fluoxetine ODT formulation has been developed and optimized successfully using Box- Behnken design and has also been manufactured efficiently using direct compression technique.