G. S. D. Gupta

Meloxicam Carbopol-Based Gels: Characterization and Evaluation

PURPOSE To formulate and evaluate the hydrogels containing meloxicam for topical application and also compare the effect of penetration enhancers on release of drug. METHODS Meloxicam gels were prepared by dispersion method using carbopol-940 and 934 (1%w/w) as rate controlling polymer and drug penetration enhancers such as tween 80, oleic acid and sesame oil in the concentration of 1% and 2% . The formulated gels were evaluated for drug content, pH, viscosity, spreadability, extrudability, in vitro drug permeation, drug release kinetics, bioadhesion test, accelerated stability of selected gel formulation. The in vitro drug permeation through pigs skin was carried out by using Keshary-Chein diffusion cell and viscosity was determined by brookfield viscometer (Modle No. LVDVE). RESULTS All the gel formulations were found to be very clear and homogeneous. Drug content of all formulations was found to be above 93%. Formulation F(14) containing carbopol-934(1%w/w) and sesame oil 2% gave 99% release as compared to other formulations obeying zero order kinetic with a good bioadhesion quality. The permeability coefficient of all formulations was found in the range of 0.2 to 0.4×10(-3)cm(2)/hr. The results were compared statistically and found with satisfactory correlation and it was observed that the rate of drug release increased with increase in concentration of penetration enhancers.

Effects of the level of dietary protein on the toxicity of hexachlorocyclohexane in rats

Male albino rats were fed for 28 days from weaning on diets containing 5% (group 1), 10% (group 2) and 21% (group 3, normal protein) protein as casein. At the end of dietary period, HCH was administered daily for 30 days to investigate the interaction between protein deficiency and pesticide toxicity. The results indicated that rats fed a lower protein diet and HCH had a higher mortality, lower rate of growth, increased liver weight and deposition of the pesticide in blood and tissues in larger amounts. Blood pressure (systolic and diastolic) was significantly increased and the heart rate showed tachycardia in low protein exposed animals. A significant increase of total lipids, cholesterol, triglycirides, free fatty acids in serum and tissues of animals exposed to low protein was observed. A close correlation existed between lipid accumulation and storage of HCH in tissues and dietary protein seemed to play an important role in detoxification.

Placental transport of lindane during early and late stages of gestation in rats

Lindane (gamma-isomer of hexachlorocyclohexane, gamma-HCH), an organochlorine pesticide, is widely used as an agricultural pesticide especially in developing countries. Human exposure is likely because of its use in some pharmaceutical preparations and in public health for pest control purpose. It has been detected in human milk and fat samples in India and in many developed countries. The accumulation of lindane over a long period in fat samples and its presence in milk suggests that the human fetus may be exposed to lindane at some time during gestation from the maternal tissue stores. The present study was, therefore, undertaken to determine the placental transfer of lindane in rats during early and late stages of gestation.

Modulation of Biochemical and Cytological Profile of Bronchoalveolar Lavage Constituents in Rats Following Split-Dose Multiple Inhalation Exposure to Methyl Isocyanate

1 Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l -1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure. 2 In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride. The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity. 3 In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF. The phagocytic potential of macrophages was, however, also decreased under this regime.

Some Neurotoxicological consequences of Hexachlorocyclohexane (HCH) stress in rats fed on protein deficient diet

Hexachlorocyclohexane (HCH), an organochlorinated pesticide used extensively for the protection of crops, has been reported to affect the central nervous system. Attempts have been made to validate the behavioural changes including distance travelled, time resting, stereotypic time, ambulatory time, stereotypic movements and vertical movements in rats treated with HCH (50 mg/kg) and fed on protein deficient diet (5% Casein) for 120 days. Significant (P < 0.001) increase of 5‐HT uptake by platelets was recorded in pesticide exposed animals. Similarly ADP induced aggregatory responses were found to be enhanced significantly (P < 0.001). Bioaccumulation of pesticide in vital organs suggest that insecticide circulate rapidly through the body and can have a rapid and definitive effect. Changes in behaviour and platelets function may also be claimed to the promising sign of neurotoxicity occurring at the lower level of pesticide exposure under the influence of malnutrition.

Influence of dietary protein deficiency on EEG neurotransmitters and neurobehaviour after chronic exposure to HCH

The problems of pesticide toxicity is of great importance where malnutrition is a rampant health problem. Rats fed on synthetic diet (21% & 5% Casein) were given orally 50 mg/Kg Hexachlorocyclohexane (HCH) for three months period. Neurotransmitters measured from the discrete areas of brain showed significant increase of dopamine (DA) and decrease in the levels of 5‐Hydroxytryptamine (5‐HT) and norepinephrine (NE). Acetylcholine (Ach) content in cerebral cortex was increased. Behavioural observations included distance travelled, resting time, ambulatory and Stereotypie movement showed marked changes on optovarimax, while a significant increase (p < 0.001) was noticed in vertical movement of the rats exposed to HCH. Electroencephalograph records showed bursts of spikes with increased wave frequency.

Effect of hexachlorocyclohexane on biochemical parameters of rats on a protein deficient diet

Male albino weanling rats were fed diets containing 5% (group I) and 21% (group II) protein as casein for 28 days. At the end of the dietary period Hexachlorocyclohexane (HCH) was administered daily for 30 days to investigate the effect of protein deficiency on the toxicity of HCH. The results indicated that rats fed a low protein diet and HCH had a higher mortality, lower rate of growth and increased liver weight. An increased glycogen and decreased glutathione level was also observed in their livers. A significant decrease in blood glucose, erythrocyte enzyme G6PD and LDH of animals exposed to low protein diet is suggestive of the disruption of the energy provision of the cell.

Effects of hexachlorocyclohexane administration on distribution of trace metals in rat tissues

The effects of daily administration of hexachlorocyclohexane (HCH) for 90 days on the distribution of Cu, Zn, Fe and Mn in rat tissues were investigated. The results indicated that HCH caused a significant increase in weight of liver and spleen and decrease in the weight of kidney, heart and brain. The spleen and heart demonstrated the maximum mobilization of metals. Comparing the individual trace elements, zinc appeared to be the most active element. None of the metals assayed registered change in RBCs but there was increase in Zn, Fe and Mn concentration in plasma.

Immunotoxic manifestations in rats following inhalative exposure to furfural vapors

Furfural is an industrial compound used as a process intermediate and as a solvent; it poses a potential inhalation hazard in occupational settings. This study was carried out to find furfural-induced immunotoxicity in Wistar rat following inhalative exposure. The weights of thymus and lymph node were found decreased, while the weights of the liver and the adrenal gland were significantly increased following furfural exposure. Delayed-type hypersensitivity response was found decreased in furfural vapors-exposed animals when compared to that of control animals. The phagocytic index of peritoneal and alveolar exudates showed significant decrease and was most prominent (90%) in 30 days-exposed groups. The number of anti-rat anti-sheep red blood cell immunoglobulin M plaque forming cells of spleen got decreased in furfural-exposed groups in comparison to control. Taken together, this study indicates that inhalation of furfural induces immunotoxic manifestations that could lead to severe immunological disorders.

Influence of cadmium on the storage and metabolism of HCH in rats

Male albino rats were administered Cd and HCH daily for six weeks to study the effect of Cd on storage and metabolism of HCH. The results indicated a marked inhibition of the metabolism of HCH in the group dosed with HCH + Cd. The metabolic rate of HCH in the group dosed with HCH + Cd was also significantly lower than that in the group dosed with HCH alone. The hepatic content of Cd and Zn was significantly increased whereas a marked depletion of Cu and Fe was observed in the groups exposed to Cd and HCH + Cd. A high level of free Cd and Zn or a low level of Fe and Cu in liver seemed to play an important role in the metabolic inhibition observed in this study.