EVALUATION OF SAFETY PROFILES OF ANURADHA OIL-AN HERBAL WOUND HEALING FORMULATION IN LABORATORY ANIMALS

Objective: To investigate Acute, Sub-acute dermal toxicity, Mucus membrane irritation activity of Anuradha Oil's (AO and AO11) – An herbal formulation having wound healing potential.Methods: The formulations were derived from Curcuma longa Linn and Glycyrrhiza glabra Linn rhizhomes,  Hamiltonia suaveolens Roxb bark,  Typha angustifolia Linn flowers,  Azadirachta indica A. Juss leaves without/with pig fat (AO and AO11 respectively)mixed in certain proportion using Sesamum indicum Linn oil as a base, manufactured at a GMP certified facility. Acute, sub-acute dermal safety, mucus membrane irritation profiles were studied by OECD guidelines number 434, 410 and 405 in Wistar rats and New Zealand rabbits respectively. For acute study dermal application of 2000 mg/kg single dose and for sub-acute study limit dose protocol of 1000 mg/kg for 28 days was used. For mucus membrane irritation test 0.10 ml dose was used.Results: In an acute study no local reaction, behavioral changes and mortality was observed at 2000 mg/kg by dermal route till 14 days. In sub-acute study with dermal application of 1000 mg/kg for 28 days, there were no abnormal signs/symptoms at the application site, no difference in body weight, food consumption, hematology/enzyme profiles, urine analysis, relative organ weights and histopathological observations of vital organs in comparison to control animals. Mucus membrane of rabbits showed no evidence of irritation for both oils.Conclusion: Acute dermal LD50 cut off for AO and AO11was found to be>2000 mg/kg, safe for dermal application for 28 days using the dose of 1000 mg/kg and non-irritant. Â

Spectrophotometric determination of tizanidine and orphenadrine via ion pair complex formation using eosin Y

A simple, sensitive and rapid spectrophotometric method was developed and validated for the determination of two skeletal muscle relaxants namely, tizanidine hydrochloride (I) and orphenadrine citrate (II) in pharmaceutical formulations. The proposed method is based on the formation of a binary complex between the studied drugs and eosin Y in aqueous buffered medium (pH 3.5). Under the optimum conditions, the binary complex showed absorption maxima at 545 nm for tizanidine and 542 nm for orphenadrine. The calibration plots were rectilinear over concentration range of 0.5-8 μg/mL and 1-12 μg/mL with limits of detection of 0.1 μg/mL and 0.3 μg/mL for tizanidine and orphenadrine respectively. The different experimental parameters affecting the development and stability of the complex were studied and optimized. The method was successfully applied for determination of the studied drugs in their dosage forms; and to the content uniformity test of tizanidine in tablets

Non-irradiation-derived reactive oxygen species (ROS) and cancer: therapeutic implications

Owing to their chemical reactivity, radicals have cytocidal properties. Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalysed reactions. Although these developments are currently still in their infancy, they nevertheless deserve consideration. There are now numerous examples known of conventional anti-cancer drugs that may at least in part exert cytotoxicity by induction of radical formation. Some drugs, such as arsenic trioxide and 2-methoxy-estradiol, were shown to induce programmed cell death due to radical formation. Enzyme-catalysed radical formation has the advantage that cytotoxic products are produced continuously over an extended period of time in the vicinity of tumour cells. Up to now the enzymatic formation of toxic metabolites has nearly exclusively been investigated using bovine serum amine oxidase (BSAO), and spermine as substrate. The metabolites of this reaction, hydrogen peroxide and aldehydes are cytotoxic. The combination of BSAO and spermine is not only able to prevent tumour cell growth, but prevents also tumour growth, particularly well if the enzyme has been conjugated with a biocompatible gel. Since the tumour cells release substrates of BSAO, the administration of spermine is not required. Combination with cytotoxic drugs, and elevation of temperature improves the cytocidal effect of spermine metabolites. The fact that multidrug resistant cells are more sensitive to spermine metabolites than their wild type counterparts makes this new approach especially attractive, since the development of multidrug resistance is one of the major problems of conventional cancer therapy