| The research on nutrient and drug delivery system is the continuation of the study on their bioactivity, for it usually can improve the in vivo bioavailability of the nutrient and drug effectively as well as reduce their toxic and side effects, making it a global research hotspot and a focus of industry competition. Gastric floating controlled release system is able to float due to its lower density than gastric juice, being rarely influenced by gastric emptying, which serves the locating purpose of drugs and nutrients who aim at releasing in the stomach. The core competence of this technology lies in the innovation of highly hydrophilic and floatable macromolecular auxiliary material and the system construction based on it.This research aims at preparing a kind of konjac gum with both floatability and controlled release properties by using a simple and safe approach with the lowest possible cost, and applying it as excipient in gastric floating controlled release system to evaluate its effect, as well as exploring the possibility to push the konjac application into the field of pharmaceutic adjuvant to cope with the fast increasing price of konjac gum.The main contents and results are listed as follow:1. Regulation of powder and colloidal properties of Konjac gum by ball-milling method. Konjac gum by different ball-mill treatment was characterized by particle size distribution, powder flowability, specific surface area, bulk density, tapped density, moisture absorption property, molecular weight, crystallization property, morphology and rheological property. It was found that after the ball-mill treatment, the dso of konjac gum fell gradually from152μm to20μm. Ball-milled konjac gum exhibited bigger repose angle and specific surface area while lower bulk density and tapped density, with4h milled konjac gum showing the best compressibility. The moisture absorption test demonstrated that konjac gum would be well stored when air humidity was lower than60%. The molecular weight of konjac glucomannan decreased from9.52x105g/mol to 4.65x105g/mol after8h ball-mill. Ball-mill treatment did not change the crystallization property of konjac gum while led to coarser surface. Reunion phenomenon occurred when the particle size was as small as20μm. The zero-shear viscosity decreased with the ball-mill treatment time, and all the rheological model applied to Cross equation.2. Construction and evaluation of konjac gum-based gastric floating system with metronidazole being the model drug. The effect of konjac gum and shell content on the release and floating properties was evaluated. The result showed the presence of konjac gum helped to reduce the drug release rate and the barrier layer also contributed to control the release rate. The particle size of konjac gum showed great influence on the release and floating properties of tablets.4h ball-milled konjac-based tablet achieved the shortest floating lag time and the best release model which applied to zero order release with the least burst release. Magnetic resonance imaging (MRI) was employed to test the water distribution in tablet during the dissolution. It was found that the4h milled konjac based tablet was more likely to form a gel-like barrier to stop water from permeating to achieve better release curve.3. Optimization and regulation of konjac gum-based gastric floating system. The4h ball-milled konjac was deacetylated by alkali and mixed with xanthan by different ratio. This mixture was used as excipient in gastric floating system with VB2as the model nutrient. It was demonstrated that K1X0-Da0achieved48h continuous zero-order release, indicating that the taking frequency of3times per day of common VB2tablet was likely to be decreased to once in2days. Further, the degree of deacetylation and the KGM/Xan ratio had a bi-directional regulating effect to the release of nutrient, foreboding that controlled release in whether short or long time can be achieved according to the release requirement of different drug and nutrient. |
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