Studies On Preparation Of Levofloxacin Sustained-release Capsules

Levofloxacin,as the third generation Fluoquinolone antimicrobial agent,is the optically pure levorotatory isomer of ofloxacin. It has a long range of antimicrobial spectrum and has showed excellent antibacterial activity against many kinds of bacteria. It is well absorbed when given orally. Meanwhile,it has a wide range of distribution in all parts of human body as well as a high bioavailability. But the common preparation of levofloxacin needs to be served frequently,leaving patients in the unconvenience completely. Therefore,the purpose of this study was designed to prepare a kind of sustained-release capsules within twelve hours which contained 150 milligrams of levofloxacin per capsule,so as to decrease the times of taking medicine and lighten the fluctuation of drug concentration in blood.HPLC method was established to determine the concentration of levofloxacin in capsules , UV method for evaluating invitro release rate of levofloxacin sustained-release capsules. Pharmaceutical preformulation studies suggested that levofloxacin has appropriate solubility and octanol/water partition coefficients which increasing with pH rising. The dissociation constant of levofloxacin having been measured is about 5.4938. Levofloxacin is stable in various of conditions,except for illumination which will reduce the content of levofloxacin gradually.An method was applicated to prepare sustained-release capsules including two processes. First,produced sustained-release granules of matrices. And then filled them in common gelatine capsule. Using ?2,the similarity factor ,as evaluating indicator,the single-factor research was utilized to evaluate the sort and amount of matrix material,filling agent and porogen. so the quantity of HPMC,starch and PVP was ascertained as the most important factors which was the key to a successful preparation manufacturing. Then the formulation of capsules was optimized by the central composite design-response surface methodology. The optimal formulation was proved proper by experiment,which has appropriate release rate in vitro. A stable enlarged process line was established to produce the levofloxacin sustained-release capsules. The quality standard of the levofloxacin sustained-release capsules was established. The study of invitro dissolution idicated that the formulation and technics applied in this research was stable and controllable,having an ability of reproducibility as well. The study of release mechanism demonstrates good fitness to Higuchi equation. The n value in Ritger-Peppas model is 0.6631,which indicates the synergy of diffusion and matrix erosion all leading the release of the levofloxacin in vitro. Moreover, the role of diffusion and matrix erosion are equal in the release process. A study of influencing factors aiming at preparations indicates that the capsules have a good stability in all kinds of extreme conditions.