INFLUENCE OF HYDRATED SODIUM CALCIUM ALUMINOSILICATE AND ACTIVATED CHARCOAL ON THE PHARMACOKINETICS OF SINGLE PULSE DOSING OF ENROFLOXACIN IN BROILER CHICKEN

ABSTRACTObjective: The present study was undertaken to evaluate the interaction kinetics of enrofloxacin, the commonly used antibacterial in poultry withmycotoxin binders namely hydrated sodium calcium aluminosilicate (HSCAS) and activated charcoal (AC), which have become inevitable componentsof poultry feed.Methods: Control group received normal feed free of toxin binder, whereas HSCAS and AC group were supplemented with HSCAS and AC at 0.5% infeed, respectively. Enrofloxacin was administered as single pulse dose (at 10 mg/kg) through drinking water to all the groups. Blood samples werecollected at predetermined time intervals after drug administration, and plasma was separated and analyzed for enrofloxacin concentrations usinghigh-performance liquid chromatography.Results: Significant decrease in area under the plasma concentration-time curve (AUC0-∞)was noticed in AC group when compared to control group(13.90±1.15 vs. 19.67±1.68 mg.h/ml), whereas HSCAS group (16.42±1.24 mg.h/ml) neither differed significantly from AC nor control group. Thevolume of distribution and clearance were significantly high in AC group when compared to control group (8.31±0.89 vs. 6.39±0.13 l/kg; 0.77±0.07 vs.0.53±0.05 l/h/kg). HSCAS group was intermediate and did not differ significantly from the other two groups (8.13±0.45 l/kg; 0.63±0.04 l/h/kg).However, volume of distribution at steady state was significantly high in both AC (10.42±1.09 l/kg) and HSCAS group (9.45±0.48 l/kg) when comparedto control group (7.21±0.20 l/kg). Maximum plasma concentration was significantly low (0.99±0.04, 0.97±0.06, 1.38±0.04 mg/ml) and time to reachmaximum plasma concentration was significantly delayed (7.33±0.42, 6.67±0.67, 4.33±0.67 h) in AC and HSCAS group when compared to controlgroup, respectively. The relative bioavailability was significantly low in both AC and HSCAS group (74.95±10.70, 88.88±15.03%) when comparedto control group. Pharmacokinetic/pharmacodynamic integration revealed that the dose of enrofloxacin (10 mg/kg) was capable of treating onlymoderately sensitive organisms (minimum inhibitory concentration ≤0.125 mg/ml) both in the presence and absence of toxin binder and higherdosage is needed for the less sensitive organism.Conclusion: The study revealed that the administration of enrofloxacin to HSCAS and AC supplemented broilers would lead to decrease in clinicalefficacy and promote the development of antimicrobial resistance. AC was found to interact more with enrofloxacin than HSCAS as observed fromthe PK parameters. Hence, careful adjustment of dosage or withdrawal of the usage of toxin binder containing either HSCAS or AC in feed duringenrofloxacin treatment is recommended.Keywords: Enrofloxacin, Pulse dosing, Hydrated sodium calcium aluminosilicate, Activated charcoal, Interaction kinetics

FORMULATION, OPTIMIZATION AND EVALUATION OF ENROFLOXACIN SOLID LIPID NANOPARTICLES FOR SUSTAINED ORAL DELIVERY

The objective of the present study was to formulate and evaluate enrofloxacin SLNs using a hot homogenization coupled with ultrasonication method. The SLNs were prepared using tripalmitin as lipid carrier, tween 80 and span 80 as surfactants and poly vinyl alcohol (PVA) as a stabilizer. The influence of factors such as concentration of lipid carrier, composition and concentration of surfactant on the particle size were investigated to optimize the formulations. The optimized SLNs formulations were utilized to entrap 0.1% enrofloxacin and characterized for particle size, polydispersity index, zeta potential (using dynamic light scattering), shape (using atomic force microscopy and transmission electron microscopy), drug encapsulation efficiency (using by dialysis and ultracentrifugation methods), and in vitro drug release (using by dialysis). The prepared SLNs were analyzed by FT-IR spectroscopy to confirm the cross-linking reaction between drug, lipid and surfactants. The results demonstrated that the particle size, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the SLNs were 154.72± 6.11nm, 0.42±0.11, -28.83±0.60mV, 59.66±3.22% and 6.13±0.32%, respectively. TEM and AFM images showed spherical to circular particles with well defined periphery. In vitro drug release exhibited biphasic pattern with an initial burst release of 18% within 2h followed by sustained release over 96h. FT-IR study suggested that during the process of formulations, lipid and surfactants have not reacted with the drug to give rise to reactant products and it was only physical mixture