Preparation Of Feisuoweima Double-Layer Sustained Release Tablets And Studies On Fexofenadine Hydrochloride Intestinal Absorption In Rat In Vitro

Fexofenadine hydrochloride (FXD) is an antihistamine with selective HI-receptor antagonist activity. Pseudoephedrine hydrochloride (PS) is an adrenergic (vasoconstrictor) agent for the relief of nasal congestion due to allergic rhinitis. Combination of the two agents is used to relieve sympotoms ofseasonal allergic rhinitis and chronic idiopathic urticaria in clinic.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.The fixed dose combination of the double-layer sustained release tablets (DLRL) with the unmodified release layer of FXD (URL) and sustained release layer of PS (SRL) was prepared. High performance liquid chromatographic method was conducted to assay the content of FXD and PS in tablets. Dissolution was also detected with the HPLC method. On the basis of single-factor tests about the influence factors on disintegration time, optimal formulation of which disintegration time was 10s±2s was obtained by orthogonal design test. The Allegra-D obtained from Aventis were used as reference tablets and their release profiles were used as standard. The similitude of the different formulations among our studies and reference tablets was evaluated with similar factor. The similar factor between one of our formulation with reference tablets was 89.2. On the basis of USL and SRL, double-layer tablets were prepared and the quality standard of tablets wasestablished. By analysis of release data from DLRL using different equations, PS released mainly by diffusion combined with erosion from HPMC matrix.Stability studies of preparation were shown that light, temperature and moisture had little effect on double-layer sustained release tablets.Using HPLC with UV detection for determining FXD and PS concentrations in plasma and using Allegra-D as the reference, the relative bioavailability and pharmacokinetics studies of FXD and PS were performed in six healthy dogs. Tmax of FXD in self-made tablets and reference tablets were 2. 7±0.8 h, 2. 5±0.38 h, respectively. Cmaxwere 603. 7±75. 8 ng/mL, 529. 2 ±93. 0 ng/mL. AUC(0-t) were 2926. 0±227. 1 ng .h /ml, 2704.5 ± 452. 3 ng .h /ml, the relative bioavailability of FXD was 109.7 %.Tmaxof PS in self-made tablets and reference tablets were 7. 7±0.82 h, 8.7±1.6 h, respectively. C maxwere 551.9±153.1 ng/mL, 506. 2±119. 4 ng/mL, AUC(0-t) ware7349. 9±1692. 6 ng . h /ml, 8660.0±2889. 4 ng . h /ml, the relative bioavailability of PS was 95.3 %. The release of PS from-DLRL in vitro correlated well with absorption fraction in vivo.The study result of the mechanism of FXD intestinal absorption by the method of everted gut sac indicated that efflux transport P-glycoprotein (P-gp) and influx transport organic anion transporting polypetide (OATP) family were involved in the absorption process of FXD through rat intestinal membrance. The P-gp inhibitors (digoxin and verapamil hydrochloride) could increase the intestinal absorption from apical (A) side to basal (B) side, and the OATP inhibitors (indometacin and diclofenac sodium) could decrease the intestinal absorption.