Formulation of enrofloxacin SLNs and its pharmacokinetics in emu (Dromaius novaehollandiae) birds

P Senthil Kumar,A Arivuchelvan,P N Richard Jagatheesan,A Jagadeeswaran,N Punniamurthy,P Mekala,P Selvaraj

doi:10.1007/s13204-014-0361-y

Abstract

The study was conducted to formulate the enrofloxacin solid lipid nanoparticles (SLNs) with sustained release profile and improved pharmacological activity and evaluate the pharmacokinetic behaviour of enrofloxacin SLNs after oral routes of administration in emus. The SLNs were prepared using tripalmitin as lipid carrier, Tween 80 and Span 80 as surfactants and polyvinyl alcohol (PVA) as a stabilizer by a hot homogenization coupled with ultrasonication method. The prepared enrofloxacin SLNs formulations were characterized for further investigation in emu birds. The pharmacokinetics of native enrofloxacin was studied after i.v. and oral bolus administration at 10 mg/kg in emu birds and compared with the disposition kinetics of enrofloxacin SLNs. Enrofloxacin and its metabolite ciprofloxacin in plasma were estimated using HPLC and the pharmacokinetic parameters were calculated by a non-compartmental analysis. The results demonstrated that the particle size, polydispersity index, zeta potential, encapsulation efficiency and loading capacity of the SLNs were 154.72 ± 6.11 nm, 0.42 ± 0.11, −28.83 ± 0.60 mV, 59.66 ± 3.22 and 6.13 ± 0.32 %, respectively. AFM and TEM 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 2 h followed by sustained release over 96 h. Pharmacokinetic results showed that the t1/2β, AUC0–∞, Vdarea/F, MRT and bioavailability were 3.107, 1.894, 1.594, 2.993 and 1.895 times enhanced (p < 0.01), while CLB and β were significantly (p < 0.01) decreased by 1.958 and 3.056 times compared to the values of native enrofloxacin administered orally. The ratio of AUC0–t cipro/AUC0–t enro after administration of native enrofloxacin and enrofloxacin SLNs was less than 10 %. The t1/2β and MRT of the metabolite were longer than those of the parent substance. The PK/PD results confirmed that the SLNs extended the enrofloxacin concentration upto 48 h against pathogens susceptible to 0.125 μg/mL in emus. The results indicated that SLNs might be a promising delivery system to prolong and enhance the pharmacological activity of enrofloxacin.

Highlights

Enrofloxacin is a fluoroquinolone antimicrobial agent developed solely for use in animals
The pharmacokinetics of native enrofloxacin was studied after i.v. and oral bolus administration at 10 mg/kg in emu birds and compared with the disposition kinetics of enrofloxacin solid lipid nanoparticles (SLNs)
Enrofloxacin and its metabolite ciprofloxacin in plasma were estimated using high-performance liquid chromatography (HPLC) and the pharmacokinetic parameters were calculated by a noncompartmental analysis

Summary

Introduction

Enrofloxacin is a fluoroquinolone antimicrobial agent developed solely for use in animals. It has potent bactericidal activity against a range of clinically relevant Gram-negative and Gram-positive pathogens as well as Mycoplasma and Chlamydiae. Bacterial infections are important causes of morbidity and mortality in domestic emus (Sales 2007). Enrofloxacin with a sustained release profile is highly convenient for use in emus. All the oral enrofloxacin formulations are available in conventional, immediate-release forms that necessitate administration twice daily or daily for several days or weeks (Martinez et al 2006). Numerous efforts have been made to develop alternative formulations of enrofloxacin to reduce the frequency of administration

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