Starch-based Aqueous Dispersion Film Coating Material And Its Releasing Behaviors

In recent years, the rapid development of modern science and technology and the update of pharmaceutical preparations theories greatly promoted the development of new drugs formulations, which pushed the study of pharmaceutical preparations from a simple-traditional form to a drug delivery system. In particular, oral sustained and controlled release delivery system has become an important direction of pharmaceutical industry due to its high drug safety and bioavailability. Development of new carrier materials and related preparation technologies, establishment of effective drug delivery systems have become an urgent tasks for the pharmaceutical industry. Based on these requirements,the development of suitable starch-based aqueous dispersion film coating sustained and controlled release carrier materials and coating technology are in line with the trend of modern drug delivery systems, and can also expand the application in the pharmaceutical field of starch, have both great scientifical importance and commercial value.Various weight-average degree of polymerization of modified starch were obtained by using high temperature and high pressure-enzyme collaborative method to meet the requirements of sustained and controlled release drug delivery systems.The structure and properties of modified starch were studied by multi-functional microscope, fourier transform infrared spectroscopy, X-ray diffraction, small angle X-ray scattering and gel permeation chromatography-laser light scattering techniques.As new film coating materials from the modified stach, the rheology, particle size, stability and other properties of the starch-based aqueous dispersion were studied according to preparation requirements and coating characteristics of aqueous dispersion film coating material. Free starch films were prepared by using cast method, the film-forming properties, moisture and digestive properties in simulated human gastric and small intestinal fluid were also studied. A suitable starch-based aqueous dispersion film coating system was developed.Using 5-amino salicylic acid and insulin as model drugs, the drugs pellets were prepared by extrusion-spheronisation. The effect of coating conditions on the coating and the release properties were investigated, the low temperature aqueous dispersion coating technology was established. The starch-based aqueous dispersion film coating sustained and controlled drug delivery system was constructed on the base of investigation of the influence of different factors on the formation of the drug delivery system and optimization of the preparation processes. The results from in-vitro tests indicated that the constructed drug delivery system was suitable for delivering not only the small molecular chemical drug but also biomacromolecule drugs, when using water as solvent, the weight average molecular weight 3.07×104g/moL of modified starch as film coating materials, solid content of 8% (w / w) ,1,2 -propylene glycol as a plasticizer and its addition level of 10%(w/w), coating weight of 30%(w/w), the drug release of approximately 28.26% in simulated gastric fluid and small intestinal fluid, after 30h the release about 90% in the simulated colon fluid, providing with good sustained and controlled performance. The release mechanism are mainly diffusion controlled release mechanism and osmotic pressure-driven coordinative mechanism, The drug release rate depends on the structure and properties of starch films, coating thickness, the molecular weight of a model drug and its solubility in the dissolution medium, the diffusion in the coating films. The established dynamic equation corresponds to zero order release kinetic model, ritger peppas equation and logistic models.The type?diabetic rat m odel and advanced im m unohisto-chemistry technology were used to validate and evaluat the releasing properties and pharmacodynamics of carrier materials as well coated pellets in the rat gastrointestinal tracts. The results suggest that starch-based aqueous dispersion film coating insulin pellets have a good drug release performance at the same effective dose of insulin, have no blood glucose fluctuations phenomenon and low blood glucose phenomenon, and have the same trend with in-vitro results.In this thesis, use high amylose corn starch which rich in nature and has good biocompatibility as a research object, good resistance to acid and enzyme properties of modified starch was obtained by physical restructuring-enzyme collaborative method. The modified starch as aqueous dispersion film coating carrier constructed film-controlled pellet delivery system and protected the physiological activity of drugs, prolonged drug release time and improve the administration effect of drug. This work not only provides foundation for aqueous dispersion coating film to meet sustained and cotrolled drug release in the digestive tract, but also provides a new way of the deep-applications of starch. Furthermore, materials from the renewable resources will be utilized as a higher value product.