Study On Konjac Glucomannan-montmorillonite Nano Composite Membrane As Colonic Drug Delivery System

Hydrogel systems of Konjac glucomannan (KGM), Polyvinyl Alcohol (PVA) and Montmorillonite (MMT) crosslinked with Sodium Tripolyphosphate (STPP) were prepared in this thesis for colon-targeting drug delivery.The amount of MMT and NaOH, the crosslinking temperature's influence to the baiance swelling and the response of the enzyme were studied. The Fourier transformed infrared spectra (FTIR), X-ray diffraction, the differential scanning calorimeter (DSC) and Mechanical Properties Testing were used to analyze the interaction between materials and the crosslinking mechanism. Using four model drugs as Berberine , Ccimetidine,Nimodipine,Hydrocortisone, the amount of MMT and NaOH's influence to the release of the drug were studied. The release mechanism was discussed and the dynamic release model was established. Then, fit the equation and discuss the parameters. The main conclusions in this paper were concluded as following:(1) In the preparing process of composite films, glycerol and PVA were used as small intercalated molecular and polymer intercalated molecular. The results of XRD, FTIR, DSC and mechanical tests showed that the M20 system (MMT: KGM = 1:5) had the strongest interaction between organic and inorganic, better compatibility between materials, the highest mechanical strength of composite membranes, less swelling degree. The system containing MMT had better response of enzyme. KGM-PVA-STPP-MMT membrane swelling follows the second Schott dynamic equation. The appropriate chemical cross-linking can improve the layer spacing and increase the dispersion of MMT. The mechanism of pattern map was given.(2) Drug release experiment showed that, because of the adsorption between water-soluble drugs as berberine, cimetidine and MMT, the encapsulation rate increased and the drug dissolution rate decreased. For water-soluble drugs, the drug dissolution rate in simulated colonic fluid was common controlled by drug solubility and hydrolyzation; while for non-water-soluble drugs, drug dissolution rate was controlled by the hydrolysis process control. So non-water soluble was more suitable for the composite films containing MMT system, the water-soluble drugs need to select less adsorption with MMT.(3) Mechanism of drug release process showed that the drug release process without enzyme meeted the Higuchi equation of drug release. In the early drug release process with enzyme, we assumed that the degradation of polymer followed the first dynamic process, in the later release process, the hydrolyzation was weakened and the release process consisted with the Higuchi equation. In short, the addition of MMT is good for the colonic drug delivery carrier, it had better response for enzyme in simulated colonic fluid, less drug loss in simulated gastric and small intestinal fluid.