Preliminary Study of the Construction of Expert System and Its Application for Liposome Preparation
|Keywords||expert system liposome polyphase proliposome silybin silybin-phospholipid complex quality evaluation pharmacokinetics bioavailability|
Expert System is a kind of software, possessing a large of knowledge and experience base on certain domain. It can solve kinds of questions in certain aspect by simulating experts’ thinking process. Because of the advantages, the expert system has applied into social life and production, and brought out fine economic benefit.With the pharmaceutics development, research of new dosage form and fresh technology will cost much time and money. However, patent right has only twenty years at most. In order to recovery cost price and obtain maximal benefits, the companies must accelerate the research speed. Under this case, the expert system on the basis of pharmaceutical theory and rich experience of experts came into being because of demand. However, the results from the recommendation of expert system may be occur mistake, because of the complex characteristics of drugs and defect of expert system. During the research of preparations, the expert system only supplies preliminary guidance, and we obtain the detail technology by means of experiment.The thesis presented here focuses mainly on the preliminary study of the construction of liposome expert system, preparation of silybin polyphase proliposome, and quality evaluation in vitro and in vivo, which may be divided into four parts.Part one: ReviewThis review includes two parts: in the first part, the composition and structure of expert system, the function, the technology and application of expert system are described. In the second part, we outlined the preparation of liposome, introduced the novel proliposome and the index of quality control. These may be regarded as a basis for our succeeding research.Part two: Initial establishment of liposome expert systemAfter looking for literature on new dosage form, accumulating experience of expert and summarizing patent messages about pharmacy, expert knowledge database including drug name, literature, help information and patent messages was constructed by appropriate method of knowledge representation. This database has abundant contents, and strong function. Therefore, we designed initially the liposome expert system. According to this expert system, researchers can obtain the experts’ guidance and patent messages. It should reduce the time and expenses, so it’s much valuable in practice.Part three: Preparation of silybin polyphase proliposomeSilybin and phospholipids formed compound with reaction to increase the solubility. Then the compound was prepared to be polyphase proliposome with the method of film carrier-oven drying. Many single factors which may influence the appearance, particle size, encapsulation efficiency and stability of liposome preparation were observed in a large scale, such as drug and phospholipids ration, phospholipids and cholesterol ration, type and quantity of surfactant, oil phase and carriers. The optimization formula was got after orthogonal experiment about principal influential factors.Part four: quality evaluation of silybin polyphase proliposome in vitro and pharmacokinetics in dogsWe observed many indexes to evaluate the quality of silybin liposome in vitro, such as the morphology, particle size, the drug loading, encapsulation efficiency, release profile, stability and so on. The results indicated that the preparation of liposome has small particle diameter, high encapsulation efficiency, and no break release phenomenon. The preparation was stable in the acid and alky solution, leaking only a few drugs. Comparing with before accelerated testing, there was no obvious change. It proved that the preparation has a fine stability.The concentration of free and overall silybin in plasma was determined after single oral administration with test and reference preparations separately, taken by the four dogs in a randomized cross-over test. The pharmacokinetics date was calculated with compartment and non-compartment model. After statistical analysis, we get the result that the silybin liposome increased the bioavailability in dogs obviously. The correlative in vitro and in vivo was well after determining the accumulation release rate with the method of Wagner-Nelson.