The Stadys On Preparation Of Time-controlled 5-ASA Controlled-release Colon-specific Pellets And Its Preparations

Colon specific drug delivery has received much interests for the last 20 years. It not only present a possibility of oral administration for therapeutic proteins and peptides, but also has some special advantages for the treatment of local disease such as inflammatory bowel disease(IBD).In present investigation, a new colon specific delivery system was developed utilizing 5-ASA as the model drug. Extrution-spherization and fluid bed technologies were adopted in the delivery system preparation.The advancement in colon-specific drug delivery and the intestinal physiological conditions in the diseased colon were reviewed, and implications of the conditions on the design of the colon specific delivery systems were discussed. Based on the relative research work available, a new multi-unit delivery system was designed. The objective release pattern of the delivery system is bimodal drug release pattern, i.e. a minimized drug release in the upper gastrointestinal tract, and a controlled-release pattern upon entry into the colon.In the pre-formulation study, the stability of 5-ASA was examined. The ultra-violet spectroscopy analytical method was established for assay and dissolution, and the HPLC method was established to determine the plasma concentration of 5-ASA in plasma.The process of preparation and the formulation of both pellets core and coated pellets were decided. The pellets containing the drug were prepared by extrusion spheronizer, then the pellets were coated with the mixture of HPMC and Aerosil as the swelling and control-releasing layer, subsequently, the outer layer of the pellets was coated with ethylcellulose aqueous dispersionSurelease as the time controlled film. The film coating operation was performed using fluid-bed coater, then the coated pellets were encapsulated with enteric capsules. The time-dependent pellets for 5-ASA controlled-release colon-specific delivery could be prepared by designing the inner swelling layer (HPMC type and ratio of the mixture) for control-releasing and outer EC film thickness for time-dependent.It was indicated the new delivery system has excellent colon specific characteristics according to in vitro dissolution experiments in combination with the study of pharmacokinetics in vivo. Less than 5％5-ASA was released from the coated pellets in the first 5 hours, and after the lag time (5 hours), 5-ASA was controlled-released from the delivery system. In vivo study of pharmacokinetics, the drug delivery index of this delivery system is 12.48.