Azithromycin In Enteric-coated Pellets, The Stomach Pellets

Azithromycin(ATM) is one of the new generation of macrolides and has several advantages over traditional macrolides such as erythromycin. It was approved for clinical use in 1992. It has a longer half life and thus can be administered once daily. Azithromycin can also achieve higher tissue concentrations and enhanced antimicrobial activity compared with erythromycin. Azithromycin has lower incidence of adverse side effects and drug interactions than other macrolides.A HPLC ultraviolet method was developed for determining the azithromycin content in pellets; a UV method was developed for the determination of ATM during the studies of physicochemical properties and release of azithromycin; A HPLC -MS method was established to monitor the plasma concentration in dogs.The results of preformulation study showed that azithromycin was soluble in acid solutions and less soluble with boosted pH value. The stability of azithromycin in several pH fluids showed that it was less stable as pH value reduced. The octanol/water partition coefficients increase with pH rising in various physiological pH fluids.Azithromycin pellets were prepared by means of power layering with the centrifugal granulation equipment. Through the formulation filtration and process observation, it was discovered that the yield of the objective pellets (32/26 mesh cut) was about 90% and the average azithromycin content was 60%. The results suggested the preparation process and formulation of azithromycin pellets can reach the expected goals.A fluid-bed spray processor was adopted for the coating of the pellets. The coating process variables were determined and controlled. The coating formula respectively composed were studied on plasticizers, anti-tacking agents, static electricity-proofing, coating level and curing time, etc. Eudragit El00 was selected for the gastric-coated pellets , Eudragit L30D-55 was selected for the enteric-coated pellets. The description of dissolution profiles for enteric-coated pellets and gastric-coated pellets suggested that the first-order became the most appropriate model to describe release kinetics.Stability studies of preparation were shown that light, temperature and moisture had little effect on enteric-coated pellets and gastric-coated pellets. The plasma concentration of azithromycin in dogs was determined by HPLC-MS method after a single oral administration of commercial tablets and self-made enteric-coated pellets. The pharmacokinetics parameters were measured. The pharmacokinetics parameters of azithromycin in enteric-coated pellets and commercial tablets analyzed by non-compartment model theory were as follows: t_max were 3.08±0.49 h and 1.00±0.45h; C₍max0 were 2.18±0.42μg/mL and 2.79±0.98μg/mL; AUC_0-96 were 44.18±3.90μg·h/mL and 39.04±6.62μg·h/mL,respectively. The result of T test showed that the self-made enterie-coated pellets'AUC_0-96 wasn't signifacantly different from the AUC_0-96 of the comercial tablets,and the former's t_max was significantly lenghthed.