Pharmacokinetics of tetracycline and tetracycline loaded nanoemulsion formula in Rabbits

Abstract

Nano-sized drug delivery systems used to improve drug pharmacokinetics especially bioavailability. Different tetracycline loaded nanoemulsions were formulated and evaluated for thermodynamic stability, morphology, droplet size and zeta potential measurements. Pharmacokinetic of TC-NE (10% Mig, 50% S/CoS and 40% water with drug concentration of 5%, w/w) was investigated in rabbits following a single oral and IV doses (50 mg/kg bwt) and compared to tetracycline HCl powder (TC-Powder) at the same dose. Tetracycline concentrations were determined in plasma samples using standard high performance liquid chromatography (HPLC) procedure. Following IV injection higher AUC0-inf (83.3 ± 4.2 and 74.8 ± 2.9 μg/ml. h) and volume of distribution (Vdss) (0.78 ± 0.06 L/kg and 0.71 ± 0.10 L/ kg) reported for TC-NE compared to TC-Powder, respectively. Furthermore, after oral administration, TC-NE was slowly absorbed and eliminated than TC-Powder with longer t1/2ka (0.518 ± 0.091 h and 0.253 ± 0.024 h) and t1/2β (4.22 ± 1.67 h and 3.33 ± 0.68 h), respectively. Moreover, the time at which maximum tetracycline plasma concentration achieved (Tmax) was 0.869 ± 0.059 h for TC--NE and 0.397 ± 0.033 h for TC-Powder. Significantly higher area under curve AUC0-t 20.4 ± 1.5 μg/ml. h and 11.1 ± 0.6 μg/ml. h and consequently higher bioavailability 29.2 ± 2.3% and 13.9 ± 0.8% was recorded for TC-NE than TC-Powder, respectively. Following oral admistiration TC-NE formula exhibited prolonged T> MIC of 10.36 ± 0.64 h compared to 7.1±0.32 h in TC-powder. In conclusion, the prepared Tetracycline loaded nanoemulsion formulation has improved oral bioavailability and prolonged the blood concentration time than TC-Powder. Further clinical studies are required to justify dosage that supports clinical efficiency.