Studies On Hydrophilic Matrix Sustained Release Tablets Of Roxithromycin

Roxithromycin is a widely-used antibacterial macrolide, which has an antibacterial spectrum in vitro similar to that of erythromycin, with strong activity against Gram-positive bacteria. The results of clinical studies with roxithromycin have confirmed the potential for its use in a variety of infections, such as respiratory tract infections, skin and soft tissue infections.Clarithromycin is also a 14-membered macrolide, about which sustained tablets have been developed now, so by comparing the physicochemical and biopharmaceutical properties between the two drugs, the author tried to find whether or not roxithromycin could be formulated into a sustained release preparation with the aims of improving its antibacterial activity in vivo, reducing adverse effects and being convenient for patients to use. Based on this, RXM sustained released tablets were designed and prepared by using HPMC as basic matrix material.According to literature, the UV method was developed for assay in vitro during the studies about physicochemical properties and release of roxithromycin and clarithromycin, the HPLC method for determining the roxithromycin content in tablets; HPLC and UV methods were developed to analyze the intestinal absorption of roxithromycin and clarithromyicn in rats; the microbiological method was established to monitor the plasma level of roxithromycin in vivo.The physicochemical studies showed that roxithromycin and clarithromycin were both diffluent in acid solutions and less soluble with boosted pH value, and either of them had a great octanol/water partition coefficient. The stability of roxithromycin in several pH fluids showed that it was less stable as pH value reduced.The absorption sites and absorption kinetics were studied from various intestinal segments ligation using the in situ perfusion method in rats. The research demonstrated that the two drugs were both absorbed well in general and better absorbed in the small intestine where there was no special absorption site. The mechanism of the intestinal absorption about both drugs was transferred to cell via passive diffusion.On the basis of pharmaceutical preformulation studies, single-factor tests were carried out and based on the influence of formulation and manufacture process on the release of roxithromycin, the optimal formulation modified to release drug over 12hr was obtained by orthogonal design tests.RXM released by the synergic effect of diffusion and erosion from HPMC matrix, and the content of either HPMC or citric acid could influence the drug release mechanism.The studies of pharmacokinetics of roxithromycin sustained release tablets in dogs indicated that compared with the conventional tablets, self-made sustained tablets were characterized by the Tmax extended by about 3 hours, Cmax reduced by nearly 30% and mean residence time (MRT) notably prolonged. Besides, the relative bioavailability was 95.01%, and there was a good correlation coefficient (0.8445) between experiments in vivo and in vitro.