| Polyelectrolyte,a new developed drug delivery system,while has many advantages,such as simple and mild preparation procedure,biocompatibility and biodegradability.excellent responsive drug release properties,and the merits to keep the bioactivity of polypeptide and proteins etc.,has attracted much attention in the field of drug controlled release.Our work includes three parts: 1. Ion cross-linked chitosan-TPP beads as a floating dosage form for the oraldeliveryThe design of an oral controlled drug delivery system (DDS) should be primary aimed at achieving more predictable and increased bioavailability of drugs. However, the development process is precluded by several physiological difficulties, such as an inability to restrain and localize the DDS within desired regions of the gastrointestinal(GI) tract and the highly variable nature of gastric emptying process.Tripolyphosphate was used as a cross-linking agent in the preparation of chitosan beads. The effect of different circumstances, including cross-linking pH ,cross-linking time ,model drugs (ranitidine) and drying method(50 ℃ oven-dried or -50 ℃ freeze-dried) , to the drug controlled release of chitosan beads were estimated. Different concentrations of TPP (5% and 10%) and Sodium Alginate (0,0.5%,0.75%,l%) was used to form the floating beads, and different cross-linking time (5min,15min,30min) was also applied. All beads were freeze-dried shows good flow properties. Scaning Electron Microscropy revealed the structure of the beads. And it was found that TPP cross-linked chitosan beads has few controlled effect on the release of ranitidine. All drug were released in 2h,faster than the beads oven-dried. In the meanwhile, although the total drug release time of freeze-dried beads was fewer, the total drug release rate and the good floating ability of the freeze-dried beads in SGF decided that freeze-dried beads may have potential as a floating dosage form for oral drug delivery system.2. The preparation of the Chitosan-Alginate pellets floating in stomachRanitidine pellets floating in stomach were prepared with chitosan using sodium alginate as cross-linking agent. The effect of drying methods (freeze dried at -50℃ or oven dried under 50℃ circumstance) on floating and release behavior of prepared pellets were investigated. Pellets were prepared with the needle dropping method. The sustained release and floating capability of ranitidine pellets were studied through the delivery test in vitro. By adjusting the formulation the floating percent of the oven-dried pellets was 100% as the expensive freeze-dried method. And the drug release time from the pellets were extended. The 4h cumulative drug release of the beads in SGF was 80%, with the floating percent about 100% at the same time. The release profiles showed that the oven-dried pellets could be a potential dosage form for oral sustained delivery in stomach.3. A floating-type oral dosage form based on multiple-unit system for prolonged gastric residenceA pre-formulation study was directed to optimize the in vitro floating ability of an Chitosan-Alginate system. For prolonged the gastric residence and drug release time of the drug , a floating-type oral dosage form based on multiple-unit system was prepared. A modified oil-in-oil (o/o) or oil-in-oil-in-water(o/o/w) emulsion solvent evaporation technique was adopted to prepare drug(5-Fu or ranitidine)-loaded PLGA microspheres. Using this modified method microspheres having various particle sizes could be produced with high drug entrapment efficiency (60%~90%). In vitro drug release tests showed a burst release of drug from PLGA microparticles, followed by a sustained release over 50 days(5-Fu) or over 2h(ranitidine). Microspheres were coated by a bead composed of a calcium alginate core and chitosan-alginate shell. The floating ability depended on the presence of the air compartment by CO2. In this way (the porous structure), beads were produced which were able to float immediately upon contact with artificial gastric juice and for a long... |
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