Stability indicating RP-HPLC method development and validation for the simultaneous determination of Sofosbuvir and Velpatasvir in tablet dosage forms

Stability indicating RP-HPLC method was developed for the simultaneous quantitation of Sofosbuvir and Velpatasvir in its pharmaceutical dosage form and validated. The drugs were separated on Discovery C18 (150mm x 4.6mm, 5μ) column using 0.01N potassium dihydrogen phosphate buffer and acetonitrile (50:50%v/v) as mobile phase on isocratic mode. The mobile phase is pump into the column at flow rate of 1.0ml/min and column oven temperature is maintained at 30ºC. The drugs were detected at a wavelength 240nm. The retention time for Sofosbuvir and Velpatasvir were found to be 2.32min and 3.34min respectively. The developed method is validated in accordance with ICH guidelines. The method was found to be accurate, precise, specific and robust. The method obeys Beer’s law at a concentration range of 100μg/ml – 600μg/ml of Sofosbuvir and 25μg/ml – 150μg/ml of Velpatasvir, with correlation coefficient of 0.999 for both the drugs. The drugs were found to be stable and less prone to degradation when they are subjected to various stress conditions

NEW STABILITY-INDICATING ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT AND VALIDATION OF LENVATINIB MESYLATE IN BULK DRUG AND PHARMACEUTICAL DOSAGE FORMS

Objective: The objective of the present study was to develop and validate a new stability-indicating method for the quantification of lenvatinib mesylate in bulk drug and pharmaceutical dosage form using ultra performance liquid chromatography (UPLC).Methods: The optimized chromatographic conditions for elution of drug included UPLC HSS C18 (100 mm × 2.1 mm, 1.8 m) column, mixture of 0.1% orthophosphoric acid and acetonitrile (50:50 v/v%) mobile phase run on an isocratic mode at a flow rate of 0.3 mL/min, 240 nm detection wavelength, and column oven temperature maintained at 30°C.Results: The retention time for lenvatinib was found to be 1.24 min. The developed method was validated for various validation parameters in accordance with the International Conference on Harmonization guidelines. The method obeyed Beer's law in the concentration range of 2.5– 15 μg/mL with a correlation coefficient of 0.9996. The percentage relative standard deviation and percentage recovery were determined to be 0.4 and 99.66–100.30%, respectively. The developed method was found to be accurate, precise, specific, linear, rugged, and robust. Forced degradation studies were conducted by exposing the drug to diverse stress conditions such as acidic, basic, peroxide, neutral, photolytic, and thermal conditions. The net degradation was obtained within the limits.Conclusion: The developed method for the estimation of lenvatinib can be employed to routine analysis of pharmaceutical dosage form

TOPICAL DRUG DELIVERY OF GOSSYPIN FROM PRONIOSOMAL GEL FORMULATIONS: IN VITRO EFFICACY AGAINST HUMAN MELANOMA CELLS

Objective: This work aimed to establish and formulate the gossypinproniosomal gel drug delivery system. Methods: Gossypin-loaded proniosomal gels (GPG) was prepared using specific non-ionic surfactants (Spans), followed by particle size (PS), entrapment efficiency (percent EE), in vitro, ex-vivo drug release, and in vitro efficacy of Gossypin against human melanoma cells (A-375). Results: The results showed that the percentage EE for the GPG is appropriate (81.3 %–95.5 %) and they are Nano-sized (189.3–912.0 nm) and the gels diffusion provided the desired sustaining effect for GPG-F7 formulation (75.5 percent). The GPG reported cell viability of 14.9±2.3 percent compared with 16.1±1.1 percent for free Gossypin at the maximum dose of 100 μg/ml for A-375 human melanoma cells after 24 hr incubation time. No major changes were seen in the percentage EE, PS of GPG after storage for 90d, in the physical stability report. Conclusion: The results obtained suggest that the proniosomal drug delivery system can enhance the flux to the skin and achieve the ideal Gossypin sustainability effect. Consequently, the use of proniosomal gel may be advantageous with regard to the topical delivery of Gossypin for melanoma treatment management

DERIVATIVE UV SPECTROSCOPIC APPROACHES IN MULTICOMPONENT ANALYSIS–A REVIEW

The spectrophotometric multi-component analysis involves spectrum recording and mathematical equations. However, spectral interference poses a major limitation when mixture samples are encountered. To overcome this derivative spectrophotometry (DS) has been introduced for the resolution of overlapping peaks. In this review modified methods like derivative quotient spectra, double divisor ratio spectra derivative method, double divisor means centering of ratio spectra method, derivative subtraction coupled with the constant multiplication method (DS-CM), amplitude subtraction (AS), modified amplitude subtraction (MAS), amplitude factor method (P-Factor), amplitude modulation method (AM), amplitude summation method (A-Sum), simultaneous derivative ratio spectrophotometry (S1DD), derivative compensation ratio via regression equation, differential dual wavelength (D1 DWL), differential derivative ratio (D1DR), successive derivative subtraction method (SDS) and derivative transformation (DT) of derivative spectrophotometry theories and applications are reviewed. These methods were applied to solve different complex pharmaceuticals mixtures. These developed methods were simple and cost-effective

Antioxidant Activity of Natural Products against Aluminium Fluoride Induced Oxidative Stress

Evaluation of antioxidant potential of natural products against Aluminium fluoride (AlF4) induced oxidative stress in albino mice were represented in the present study. Gossypin, Quercetin dehydrate, (-)-Epicatechin gallate, Gallic acid and Suramin sulphate (G-protein inhibitor) were evaluated for antioxidant activity by measuring various biochemical / enzymatic markers such as lipid peroxidation, glutathione, total thiols, catalase and  superoxide dismutase. Exposure to Aluminium fluoride resulted in the oxidative stress and free radical mediated damage. The flavonoids like Gossypin, Quercetin, (-) -Epicatechin gallate, Gallic acid and Suramin sulphate are significantly reduced lipid peroxidation, reversed the reduced protective enzymes SOD,CAT and non-enzymatic like glutathione and total thiols levels were approached to normal levels in Aluminium fluoride  exposed mice. All the test compounds were showed significant protectionagainst fluoride toxicity. Results of the present study reveals that the flavonoids and Suramin sulphate showed significant antioxidant activity on Aluminium fluoride induced oxidative stress. Further research warranted to study their exact mechanism of action

Anti-inflammatory and Analgesic Activities of Amorphophallus bulbifer (Roxb) Kunth Whole Plant

Purpose: To investigate the anti-inflammatory and analgesic activities of the Amorphophallus Bulbifer in Wistar rats and mice.Methods: The anti-inflammatory activity of the hydroalcohol extract of A. bulbifer whole plant at dose levels of 100 and 200 mg/kg p.o. in rats was determined with a plethysmograph paw volume difference of the animals pre- and post-treatment. Ibuprofen (10 mg/kg) was employed as reference standard. Analgesic activity was evaluated using tail flick and tail immersion techniques, by measuring the reaction time of the animals treated with either standard or extract. Pentazocin (30 mg/kg) was used as reference standard.Results: The extract showed significant anti-inflammatory and analgesic activities at the two test dose levels at the 4th hour (p < 0.001). The extract exhibited anti inflammatory activity of 56.5 (p < 0.001) and57.1 % (p < 0.001) inhibition compared to the control group in the carrageenan and histamine-induced inflammation model at a dose of 200 mg/kg. For analgesic activity, the extract showed reaction times of7.33 (p < 0.001) and 7.83 (p < 0.001) min in the tail flick and tail immersion models, respectively, at a dose of 200 mg/kg while the normal and reference groups exhibited reaction times of 2.16, 2.66 and8.16 (p < 0.001) and 8.5 (p < 0.001) in the tail flick and tail immersion methods, respectively.Conclusion: Based on the findings, it can be concluded that  Amorphophallus bulbifer possesses antiinflammatory and analgesic properties and this lends some support for its use in traditional medicalpractice.Keywords: Amorphophallus bulbifer, Anti-inflammatory activity, Analgesic activit

Genetic Reconstruction of Protozoan rRNA Decoding Sites Provides a Rationale for Paromomycin Activity against Leishmania and Trypanosoma

Aminoglycoside antibiotics target the ribosomal decoding A-site and are active against a broad spectrum of bacteria. These compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16S rRNA. One particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by Leishmania spp. The precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic and/or the mitochondrial protozoan ribosome. To establish an experimental model for the study of protozoan decoding-site function, we constructed bacterial chimeric ribosomes where the central part of bacterial 16S rRNA helix 44 has been replaced by the corresponding Leishmania and Trypanosoma rRNA sequences. Relating the results from in-vitro ribosomal assays to that of in-vivo aminoglycoside activity against Trypanosoma brucei, as assessed in cell cultures and in a mouse model of infection, we conclude that aminoglycosides affect cytosolic translation while the mitochondrial ribosome of trypanosomes is not a target for aminoglycoside antibiotics