Studies On Fexofenadine Hydrochlorid Sustained-release Tablets

Fexofenadine, the primary metabolite of terfenadine, is a selective and peripherally acting H₁ receptor antagonist and is being developed as a non sedating H₁ antihistaminic drug, In clinical studies it is used for the treatment of seasonal allergic rhinitis and chronic urticaria without producing sedation.In this paper, fexofenadine hydrochlorid (FXD) was selected as the model drug to prepare matrix sustained-release tablets. And the drug release character and mechanism were studied. At last, the pharmacokinetics study of FXD sustained-release tablets was performed.Basic physicalchemical properties and the stability of FXD were investigated. FXD was sparingly soluble in phosphate buffers at physiologyical pH condition and stable at high temperature, moisture. It was shown that the drug was insensitive to oxygen and light.A sustained released tablet of once daily administration was designed. High performance liquid chromatographic method was conducted to assay the content of FXD in tablets. Dissolution was also detected with the HPLC method. In the formulation study of FXD sustained-release tablets, hydroxypropyl methylcelluse (HPMC),lactose and microcrystalline cellulose (MCC) were used to make the tablets. The effects of many factors including formulation and technique on the release behavior of tablets were investigated. Based on the results of single factor tests, an optimal self-prepared FXD sustained-release tablets was screened and according to addenda XIXD of CHP2005 the quality standard of tablets was established. The results of quality studies on self-prepared FXD sustained-release tablets showed the homogeneity of one batch and the repeatability of three batches were good.By analysis of release data from FXD sustained-release tablets using different equations, the in vitro drug release mechanism was confirmed as the combination result of matrix erosion and drug diffusion. Stability studies of preparation were shown that light,temperature and moisture had little effect on sustained released tablets. With the self-made FXD conventional tablets as the reference, the pharmacokinetics study of self-prepared FXD sustained-release tablets was performed in eight Beagle dogs. With crossover design, a HPLC method with UV detection was employed to detect the drug concentration in plasma of Beagle dogs administered with single dose. The pharmacokinetics parameters of the test and reference tablets were as follows: t_max were (13.5±0.5) h and (2.6±0.2) h; C_max were (662.1±28.4) ng·mL^-1 and (977.4±19.8) ng·mL^-1; AUC_0-48 were (5178.9±146.0) ng·h·mL_-1 and (4841.9±485.5) ng·h·mL^-1; AUC_0-∞ were (5397.3±172.4) ng·h·mL^-1 and (5089.0±510.0) ng·h·mL^-1, respectively. The relative bioavailability of FXD sustained release tablets with respect to refence conventional tablets was 107% from the AUC_0-t measurement. Bioequivalence was observed between the two formulations. The results of judgement showed that the in vitro release of self-made FXD sustained release tablets was correlative well with absorption fraction in vivo (r=0.9527).