Studies On Azithromycin Sustained-Release Tablets

Azithromycin is one of the new macrolides which has been widely used in the treatment of respiratory tract infection,skin and soft tissue infections,urogenifal infection.Because of its gastro-intestinal side effects,the further development of its oral preparation and clinical application was restricted.It is necessary to develop a sustained-release formulation of azithromycin with good bioavailability and stability to reduce the frequency of administration, side-effect and the fluctuation of drug plasma concentration to improve patients’ compliance.According to the literature,the UV spectrophotometry method for the determination of azithromycin release properties in vitro,the HPLC method for determination of drug content in tablets were developed.And the HPLC-MS method for the analysis of drug concentration in dog plasma was set up.The methods were quick and accurate which could meet the requirement of the analysis.In this paper,insoluble medicine azithromycin was selected as a model drug to study the effect of three different matrix materials,HPMC,sodium alginate and polyethylene oxide on drug release.Similarity factors（f₂）were employed as the evaluation standard to optimize the formulation of the sustained release tablets prepared by the three different polymers as matrix materials.The quality studies on self-prepared sustained release tablets showed that the drug release speed was influenced significantly by pH value of dissolution solution and the rotation speed of the baskets,but little affected by hardness of the tablets.Drug release homogeneity and repeatability of self-prepared sustained release tablets were satisfactory.The mechanism of drug release in vitro was confirmed as the combination result of drug diffusion and matrix erosion. Stability studies of azithromycin sustained release tablets showed that high temperature and light had little effect on the content and release behavior of the drug,but the tablets absorbed moisture in the RH 92.5%condition.With the commercial azithromycin dispersible tablets as the reference formulation,the pharmacokinetics of self-prepared azithromycin sustained release tablets（F2）in vivo was studied with six dogs,which was determined by the method of HPLC-MS.The pharmacokinetic parameters of the reference tablet were as follows:AUC_0-144(μg·h·mL^-1)was 82.45±14.83,C_max (μg·mL^-1)was 4.37±0.66,T_max（h）was 1.58±0.20.And the pharmacokinetic parameters, AUC_0-144,C_maxand T_maxof the self-prepared azithromycin sustained-release tablets were（91.45±13.46）μg·h·mL^-1,（3.54±0.40）μg·mL^-1,（4.33±0.52）h,respectively.The relative bioavailability of test formulation to reference formulation was 117.4%.The results in single-dose studies revealed that the two formulations is bioequivalent by AUC_0-144,but not bioequivalent by C_max.