Pharmacokinetics of Tetracycline and Tetracycline Loaded Nanoemulsion Formula in Rabbits

摘要

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.