Studies On Lung Targeted Microspheres Of Enrofloxacin

Enrofloxacin, an antibacterial drug marketed specifically for animal use,has broad-spectrumactivity, including Gram-negative and some Gram-positive bacteria. Enrofloxacin is useful for the treatment of several animal bacterial disease and mycoplasma penumonia. Encapsulation of enrofloxacin in microspheres are used to improve efffectivenss of the drug in the treatment of bacterial infections and to alter some pharmacikinetic properties by inravenous administration. An optimum procedure was established for preparing lung targeting enrofloxacin miscrospheres by the method of enmulsification-congealing method. The appearance, particle and size distribution, ENR content, in vitro release,stability determination of enrofloxacin in rabbit and lung-targeting characteristics were studied in the paper.Enrofloxacin was chosen as model drug, biodegradable gelatin was used as a carrier materal ,liquid paraffin as the oil phase,Span-80 as the emusifier. The orthogonal test methods was also used to optimize the preparation condition of the blank gelatin microspherers. Furthermore , Lung targeted microspheres of enrofloxacin were preparation by using the emulsifying technique. The results indicated that arithmetic mean diameter of ENR-GMS was 12.35 u m with 92% of the ENR-GMS range from 7.0 to 30 P m. The drug content in the microspheres was determined by ultraviolet spectrophotometry. The average ENR-GMS entrapment efficiency was 43.62% and the quantity of load-drug was 20.67%. Release of the drug from ENR-GMS in vitro remarkably became slower than that of ENR and its t]/2 was 6 times longer than that of ENR. The dissolution profiles of the ENR-GMS followed Higuchi kinetics. The release rate of enrofloxacin in vitro showed that the ENR-GMS had pronouncedly sustained-release effect. The study on the stability of the ENR-GMS included the light accelerated test and thermal stress test. All characteristic such as color, particle and size distribution, ENR content and decomposed product had no significant changes.The experimental results indiacated that the preparation had good stability.Plasma and tissue ENR were determined by HPLC-FLD,The standard curve for ENR was linear in a range of 10¹000ng/ml, r=0.9993, n=5.Recoveries were more than 70% for ENR with 30 300ng/ml fortified samples.The coeffient of variation were less than 6%. In the research of pharmacokinetics, a single dose of ENR injection and that of the ENR—GMS injection were given to 22 rabbits by intravenous administration, pharmacokinetic analysis was carried out by using a computer program(3P97,China Pharmacolohy Association).The distribution test in rabbits indicated that the lung targeting effect of the ENR—GMS was obvious. After ENR was prepared to microspheres, Targeting efficacy (te) of the lung compared to blood and other tissues all were more than 1.0, ENR-GMS significally alter the distribution of enrofloxacin in rabbits.Compared to other organs and blood the targeting efficiency of the lung increased 1.6 to 4.92 times.The Kinetics of the ENR ingection and ENR-GMS injection in rabbit lung after intravenous injection was best accordingly described by two-compartment open model and three-compartment open model.T_1/2αand T_1/2β of the ENR-GMS were extended, its T_max was delayed, CL(s) was reduced by 52.2 % .ENR-GMS had a good targeting efficiency.