Zahid Iqbal

Analysis of different toxic impacts of Fipronil on growth, hemato-biochemistry, protoplasm and reproduction in adult cockerels

Abstract Fipronil (FIP), a broad-spectrum phenylpyrazole, is extensively used across the globe to control pests and as a veterinary drug. Incorrect use of FIP leads to contamination of soil and water ultimately causes toxic effects in non-target organisms. Therefore, the present experimental study was aimed to determine the deleterious effects of sub-lethal concentrations of FIP in adult cockerels. FIP mixed in corn oil was administered orally in different groups as follows: A = control, B = 1.5 mg/kg, C = 2.5 mg/kg, D = 3.5 mg/kg and E = 4.5 mg/kg body weight for 60 d. Signs of toxicity like anemic comb, tremors, gasping and watery droppings were evident in birds exposed to higher levels. The feed intake, body weight, absolute and the relative weight of different organs were significantly (p ≤ .05) decreased in birds exposed to higher concentrations. Histomorphometric analysis of small intestine in birds exposed to higher levels of FIP showed decreased villus height and crypt depth of duodenum, jejunum and ilium. Histologically, congestion in liver, pyknosis of hepatocytes and congestion in kidneys along with necrosis of tubular epithelial cells and increased urinary spaces were observed in birds. Microscopically, seminiferous tubules exhibited necrotic nuclei of the spermatids, arrest of process of spermatogenesis and admixture of necrotic cells in testes of exposed birds. Moreover, significantly (p ≤ .05) decreased hematological parameters such as erythrocytes counts, hemoglobin concentrations and hematocrit, while increased total leukocyte counts were recorded in birds. Furthermore, significantly (p ≤ .05) increased concentrations of serum urea, creatinine, alanine aminotransferase, aspartate aminotransferase and cardiac isoenzyme (CK-MB), while reduced serum testosterone levels were recorded in birds. Results revealed significantly (p ≤ .05) increased frequency of micronuclei in erythrocyte and bone marrow cells. The findings of our study demonstrated that FIP induces deleterious impacts on multiple tissues in birds even at low doses.

PHARMACOKINETICS AND DOSAGE REGIMEN OF CIPROFLOXACIN FOLLOWING SINGLE INTRAMUSCULAR ADMINISTRATION IN NILI/RAVI BUFFALOS

Ciprofloxacin is second generation fluoroquinolone antibiotic which is being used to treat various infectious diseases of man and animals. Due to wide-spread use of this antimicrobial in veterinary clinics, but little information regarding its disposition, this project was carried out to determine the PK and optimal dosage regimen of ciprofloxacin in Nili/Ravi buffalos. Eight healthy adult buffalos of Nili/Ravi breed (average ± SE weight of 368 ± 44 kg) were maintained under same conditions of environment and management. A dose of 5 mg/Kg was administered in the neck muscles of each animal through injection. After injecting drug, samples of blood were taken at various times and kept in centrifuge tubes having heparin. In every animal, a control sample of blood was drawn before injecting drug. HPLC was used to determine drug concentration in the samples. The value for half life elimination (t1/2 s) was 3.05 ± 0.20 hours. Mean ± SE value for volume of distribution (Vd) was 1.09 ± 0.06 L/kg, for AUC was 20.28 ± 1.13 µg.hr/ml and for total body clearance (CL) was 0.25 ± 0.02 L/hr/kg. An optimal dosage regimen for intramuscular administration of ciprofloxacin in Nili/Ravi buffalos was calculated using these parameters which was 17.86 mg/kg, recommended to be given after every 24 hours. We came to conclusion that our calculated dose in local buffalos was significantly higher than the recommended dose of manufacturer and to avoid antimicrobial resistance, this locally investigated dosage regimen should be strictly followed in local buffalos.W Biopharma products going offpatent and guidelines for cost effective Biosimilars being defined globally, there is a strategy that major biopharma companies need to adopt to counter this prevailing inclination of towards Biosimilars. Biologics have been offering solutions where small molecule drugs have failed to reach. The Biopharma addressed areas like cancer, arthritis are the areas of concern whose treatment was long awaited. Following a period of decline in new chemical entities they provided a much needed injection of innovation to drug treatment. The Biologics market was valued to be 108 billion USD for the year 2011 and is expected to grow at CAGR of 8% to 160 billion USD for the year 2016. Growing with this market is another market which is not something that Innovator biologic producer wants but they have no other go on the account of the product hitting the patent expiry period. They should adopt strategies to either retain the exclusivity or join the stream of growing biosimilars.The aim and objective of the present investigation describes the development and evaluation of chitosan based Interpenetrating polymeric network of hydrogel beads for modified release of simvastatin. A Box benhken design was employed to design Interpenetrating polymeric network of hydrogel beads of simvastatin by precipitation technique. Simvastatin has less solubility in water hence effort is to increase the solubility by forming an inclusion complex (1:1) with beta-cyclodextrin and then incorporate in to polymer bland. This effort also protects the drug from solvent and crosslinker effect during preparation. The effect of critical formulation variables namely amount of polymers, concentration of glutaraldehyde, and time of crosslinking on % drug entrapment, beads diameter, swelling and in-vitro % drug release was investigated using response surface methodology. The response parameters were statistically analyzed. The parameters were evaluated using the F test and mathematical models were generated for each response parameter using multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). The three main factors studied had a significant effect (P<0.05) on response variables. The optimized formulation showed 91.12 cumulative percentage releases in duration of 12 h following zero order kinetics. The % drug entrapment, area increased after swelling study and beads diameter were found to be 78.51%, 35.0 mm2 and 1.22 mm2 respectively. The mechanism of drug release was characterized by Higuchi diffusion model. The experimental values of the response parameters were in agreement with those predicted by the mathematical models confirming the prognostic ability of MLRA and ANOVA. Optimized formulation further process for various instrumental study such as scanning electron microscopy (SEM) and trinocular optical microscopy to study surface morphology of beads. Fourier transform infrared spectroscopy (FTIR) study and differential scanning calorimeter (DSC) are used to confirms the crosslinking, stability of drug in the formulation, to confirm the formation of inclusion complex, characterization of drug and polymers as well as drugexcipients compatibility. Stability study on optimized formulation also performed as per ICH guideline for 6 week. It is concluded from results data that the prepared formulation fulfil the aim of the work.