Font Size: a A A

The Evaluation Of Carboxymethyl Chitosan Microspheres Containing Levofloxacin For Colon-specific Drug Delivery In Vitro And In Vivo

Posted on:2005-12-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:1104360125968314Subject:Surgery
Abstract/Summary:PDF Full Text Request
[BACKGROUND)Specific targeting of drugs to the colon is recognized to have several therapeutic advantages. Drugs which are destroyed by the stomach acid and/or metabolized by pancreatic enzymes are slightly affected in the colon, and sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Treatment of colonic diseases such as ulcerative colitis, colorectal cancer and Crohn's disease is more effective with direct delivery of drugs to the affected area. Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes. A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, guar gum, amylose and locust bean gum. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side-effect profiles and may improve patient compliance.[OBJECTIVES]The aim of our study was to develop a levofloxacin drug orally administered carrier system based on CMC to provide colon-specific delivery drug for colon infections therapy and use as anti-inflammation drug for army.1. To prepare LVFX/CMC and LVFX/CBM gels. Detect the physical and chemical characteristics of those gels and evaluate in vitro release of this dosage form in artificial medium of stomach, small intestine and large intestinal.2. Detect the physical and chemical characteristics of LVFX/CMC microspheres and evaluate in vitro release of this dosage form in artificial medium of stomach, small intestine and large intestinal.3. Evaluate in vivo release of LVFX/CMC microspheres in rats. Detect the concentration of LVFX in the stomach, intestine, cecum, colon and blood of rat respectively after the administration of LVFX/CMC microspheres. Investigate the changes in cecum and colon endotoxin after the administration of LVFX/CMCmicrospheres.[METHODS]1. Prepared CMC and CBM934P gels with LVFX respectively and the release of them in artificial medium of stomach , small intestine and large intestinal was studied in vitro. The quantity of the released substance was determined by UV-spectroscopy.2. Microspheres were achieved by emulsification and cross-linking process. Physical and chemical characteristics of microspheres were detected using scanning electron microscopy (SEM) and other methods. The release in artificial medium of stomach , small intestine and the large intestinal was studied in vitro. The quantity of the released substance was determined by UV-spectroscopy.3. In vivo release studies of LVFX/CMC microspheres was in rats. The stomach, intestine, cecum, colon contents and plasma was obtained after LVFX/CMC microspheres adminstration. The contents of LVFX in various samples were determined by HPLC. The degradation of the LVFX/CMC microspheres in those medium was evaluated by scanning electron microscope (SEM). The endotoxin levels of various samples were detected by limulus ameobocyte lysate (LAL) .[RESULTS]1. CMC and CBM934P gels with LVFX were prepared . The accumulative release of LVFX/CMC gels was 10.68% within Ih in artificial medium of stomach and 28.64% in artificial medium of small intestine in 2h, while the release reached to about 100% for LVFX/CMC gels in the case of the large intestinal liquid for 4h. The accumulative release of LVFX/CBM934P gels was 33.36% within Ih in artificial medium of stomach and 48.69% in artificial medium of small intestine in 2h, while the release reached to about 78.91% for LVFX/CBM934P gels in the case of the large intestinal liquid for 4h.2. The accumulative release of LVFX/CMC microspheres was 8.62% within 2h in artificial medium of stomach and 29.39% in artificial medium of small in...
Keywords/Search Tags:Carboxymethylchitosan, Colon-specific drug delivery, Levofloxacin, Microspheres, HPLC, LAL.
PDF Full Text Request
Related items