Preparation And Evaluation Of Tilmicosin Encapsulated In Liposomes

Tilmicosin is a macrolide antibiotic for veterinary use only,which has a broad spectrum in therapy,but it also has a certain cardiac toxicity and kidney toxicity,which limits its clinical application more or less. Lioposome,as a kind of targeting drug delivery system,has the advantages of targeting,low toxicity and outstanding effect.To decrease the toxic side effect,the liposomal tilmicosin is prepared.The thesis presented here focuses mainly on the preparation of the tilmicosin liposome and its quality evaluation,which may be divided into the following four parts.Part one:ReviewsIn this review,we introduced the relevant basic theories of liposome as a drug carrier,including the preparation of liposome;the mechanism of liposome as a drug carrier;and the application of liposome as a drug carrier.Lay the foundation for the follow-up experimental study.Part two:The Performulation Study of Tilmicosin liposomesIn the study,HPLC determination was developed for tilmicosin in vitro and it was validated by characterization of linearity,precision as well as accuracy.PBS(pH 7.4) was used to elute liposomes and then methanol solution was applied to destroy the structure of liposomes.The tilmicosin in methanol solution and free tilmicosin was respectively determined by HPLC,then encapsulation efficiency(EE) was calculated.Part three:Preparation of Tilmicosin LiposomesThis study developed a pH gradient method for encapsulating tilmicosin into liposomes.The effect of different formulation factors on the encapsulation efficiency(EE) and the size of tilmicosin liposome were investigated.These factors included the amount of soybean phospholipid,the amount of cholesterol,the ratio of drug to soybean phospholipid,the ratio of cholesterol to soybean phospholipid,the incubation temperature and time.By the orthogonal design,the EE (96.9%) was obtained when using tilmicosin 30mg,soybean phospholipid 600 mg and Chol 150 mg at 0.30 M citrate-sodium citrate buffer(pH 4.0). In order to improve the stability of tilmicosin liposomes,freeze-drying with 2.5%sucrose and 2.5%lactose as cryoprotectant was carried out to achieve long-term stability.Part four:Quality Evaluation of Tilmieosin LiposomesPhysicochemical property,release in vitro and stability were studied to evaluate the quality of tilmicosin liposomes.As a result,the hydrated liposomes appeared to be global vesicles,the particle size of them was well distributed.The release of liposomes in vitro was well fitted with the first order kinetics equation,compared with the solution of crude drug,the hydrated liposomes of tilmicosin had a certain delayed release effect;the influencing factor test of stability showed that the lyophilized powder was sensitive to temperature,illumination,and it was also affected by humidity,therefore,it should be stored in low temperature,in sealed condition,and away from light.