Font Size: a A A

Study On The Release And Absorption Of Colon Site-Specific Dosage Forms Triggered By Colon Bacteria-Releasing Enzymes

Posted on:2005-08-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:G F LiFull Text:PDF
Abstract/Summary:PDF Full Text Request
Colon site-specific drug delivery system, mainly including time-controlled release and pH-dependent form as well as bacterial-triggered form, is being extensively investigated in the pharmaceutical area. However, due to considerable variations in transit time and pH in the digestive tract depending on diet, food intake, intestinal motility and disease states, the more attention has been paid to the bacterial-triggered form in recent years. Under these circumstances, I shaped my research in which, recombinant human colony-stimulating factor (rhG-CSF), 5-aminosalicylic acid (5-ASA) and dexamethasone sodium phosphate (DSP) were chosen as 3 model drugs, and the colon site-specific drug dosage forms of these drugs were prepared, as chitosan, one of materials which can easily be degraded by the colon bacteria-releasing enzymes, was used as the main carrier. Then the characteristic of the dosage forms was evaluated with the in vitro and the in vivo release and absorption experiments.The gastrointestinal absorption of rhG-CSF, one of peptide and protein drugs, is generally poor after oral administration. This poor absorption has been attributed to the extensive hydrolysis of rhG-CSF by the proteolytic enzymes and its poor membrane permeability characteristics in the upper gastrointestinal region. However, the level of the colon proteolytic enzymes is the lowest in the whole gastrointestinal tract and drugs can stay much longer in this region. Also, macromolecule substances permeate more easily into the colon wall. Hence, the oral administration of rhG-CSF colon site-specificchitosan capsule may be a chance to exert the effects of the drug, which is not13reported so far in the publications. Superior to many other dosage forms, the absorption enhancer can be filled in this special capsule and reaches the colon with rhG-CSF at the same time after oral administration, and more rhG-CSF then is absorbed with the synergism.5-ASA is a widely prescribed drug for the treatment of inflammatory bowel disease, ulcerative colitis, and Crohn's disease, its treatment effect dependent on the level of 5-ASA in the local colon wall. However, the drug is easily absorbed into the circulation after its common preparation is taken orally. Thereafter, some severe side-effects come into being. Based on these findings, it is very useful to develop its colon site-specific drug dosage form. Hence, 5-ASA colon site-specific chitosan capsule was investigated in the dissertation, which is not yet reported so far in the domestic publications.Similar to the 5-ASA, DSP also exerts its treatment effect on inflammatory bowel disease, ulcerative colitis, and Crohn's disease, which is related to the local DSP concentration in the colon. Generally speaking, DSP is rapidly absorbed into the blood after oral administration and the distribution in the colon is not high. Though increasing the level of DSP in the treatment region, some of the side effects associated with glucocorticosteroid pharmacotherapy can not be avoided by increasing the dose, some even causing death if administrated for a longer period. Another administration of DSP is by the coloclysis in the treatment of these diseases. However, it is not convenient for chronic patients because the administration must be conducted with the help of doctor, And this method is not effective on the ascending or transverse colon due to the limitation of coloclysis technique . On the other hand, many investigations show that the drug-carried liposome can significantly increase the drug local bioavailability if the liposome is directly administrated on the diseased regions such as skin, eye, mouth and rectum.14Hence, a new idea was proposed in this doctorial dissertation: If DSP-carried liposome is filled in the colon-specific chitosan capsule and the liposome is released in the colon after oral administration of the capsule. Then, DSP may exert more effective treatment while more less absorption into the circulation. So far, study on the absorption and distribution of drug-carried liposome in the c...
Keywords/Search Tags:Recombinant human colony-stimulating factor, 5-Aminosalicylic acid, Dexamethasone sodium phosphate, Chitosan capsule, Liposome, In vitro Ussing Chamber, Colon site-specific delivery
PDF Full Text Request
Related items