| In recent years, more and more scholars pay attention to sustained release drug delivery system, as a novel drug delivery system, for it can destination control the drug release and reduce the frequency of administration in order to achieve the purpose of treatment. Now it has become one of the hottest focuses in oral solid preparations. Silybin is a traditional Hepatoprotective cholagogue drug that is used clinically for the treatment of acute and chronic hepatitis, it need for long-term use, various liver damage, liver fibrosis, early cirrhosis, gallstones and spleen disease and so on. In order to get effectiveness quickly and keep long impact, silybin double-layer tablets with immediate-release layer and sustained-release layer are prepared.In this article, we mainly studied the basic physical and chemical properties of silybin and several characteristics of SLB double-layer tablets, including formulation and design, the drug release mechanism, initial stability experiment and quality standards.Firstly, the High-performance liquid chromatography (HPLC) methods were established for content determination and related substances of silybin double-layer tablets. Ultraviolet spectrophotometry (UV) method was determined for the investigation of solubility and oil-water partition coefficient and drug release in vitro. The basic physical and chemical properties of silybin and the initial stability of bulk drug and compatibility experiments were inspected to lay the foundation for the formulation design.The optimal technology and formulation of silybin solid dispersion were selcted on the influence factor experiments such as carrier type, the vector molecular weight, the amount of carrier, the joint carrier, a surface active agent and a method for drying by using solvent-melting method. X-ray diffraction (XRD) analysis exhibits that the thermal characteristic of silybin is sheltered and the solid dispersion was in an amorphous form. Stability studies of silybin solid dispersion showed that the stable to light, room temperature and40℃high temperature, slightly hygroscopic at RH75% humidity, traits and dissolution almost on change, so it need to be stored in a moisture-proof container.Immediate-release layer of silybin were prepared by powder depressed directly technology. The best formulation and preparation routes of the immediate-release layer were optimized by the single factors and orthogonal experimental design using the cumulative dissolution profile and the dissolution at30minutes as indicators. Preparation technologies affecting the dissolution were studied. Sustained-release layer of silybin were prepared by wet granulation pressed method. Using the cumlative release of each time point and the release profile as indexs, by the single factors and central composite design-response surface methodology to optimized the prescription of the sustained-release layer based on the homogenous factor (f2) and comprehensive scoring method, and verified it. On the basis of immediate-release layer and sustained-release layer, double-layer tablets were prepared and the quality standard of tablets was established. By analysis of cumulative release data from the double-layer tablets using different equations, the combination results confirmed that the drug release mechanism of the double-layer tablets mainly by diffusion combined with erosion.Lastly, based on the study of preparation, initial quality standards study was put forward. The result displayed that drafts of quality criterion for double-layer tablets could well control the quality of products. The preliminary stability studies of silybin double-layer tablets indicated that light, temperature were stable on the traits, hardness, contents, related substances and release behavior of drug; in addition to a slightly moisture absorption, the other indicators were normal when the double-layer tablets under the humidity conditions. It should be sealed and stored in a cool place desiccant. |
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