Chinese Medicine Microemulsion Drug Carrier System, Key Technology Research

Mecroemulsion is a new drug delivery system which emerges recently. Mecroemulsion is a thermodynamics resistant homogeneous phase system which is composed of oil-water-sufactant-consurfactant, it is transparent or similar transparent in appearance, also, this system has two forma-- water-in-oil and oil-in-water, which is the same with normal emulsion, but microemulsion's particle diameter is small which is between 10nm and 100nm, therefore, it is also named nanoemulsion. Microemulsion is different from emulsion, it is transparent in appearance, small in particle diameter, low in viscosity, stable in thermodynamics. Contrast to microemulsion, emulsion's particle diameter is always larger than 100nm, and it will be layering after long time place or centrifugate. Microemulsion is also different from glue ball, the latter is outclass than the former in the content of disperse phase. Exactly because of these characteristic, people think highly of microemulsion as a drug delivery. Microemulsion has tremendous applying potency as a new drug delivery which has the following advantage.(1) Microemulsion can elevate the solubility of insoluvility drug and decrease the dosage of this kind drug.(2) Microemulsion has small particle diameter, because of this, it can pass gastrointestinal tract epithelial cells effetely and rapidly, improve the drug's bioavailability.(3) Microemulsion is suit for many routes of administration, such as oral drug administration, injettion and cutaneous drug administration.(4) The method to preparation is simple once the formula is determined.The purpose of this research is to investigate the key problems of microemulsion applying in Chinese herbal drugs, and settle the basic skills for the applying of mecroemulsion generally. The contents of this research compose the following four chapters.1. The key skills in preparation of mecroemulsionThis chapter researches the key skills to prepare Chinese herbal drug microemulsion in four aspects: single active component, active component formula, single Chinese herbal drug and compound recipe. The most important point is the course of formula bolting, suitable tools and methods can simplified this process. This article use titration assisted by computer software(MEPDplot) which is designed independently to bolting formula, it has been proofed that this method is easy to do and can get the phase diagram access to the real situation, it also can cut down the workload in formula bolting. When prepare the active component and recipe microemulsion, the most important point is to select suitable phases, it has been desired few usage of adjuvant and great solubilization to main drug as far as possible. When to prepare single Chinese herbal drug and recipe microemulsion, on one hand is to select suitable method to extract and depurate the water solubility and oil, on the other hand is to select suitable surfactant and cosurfactant, which desired these two can assist the extracted water solubility and oil from Chinese herbal drug to form microemulsion. In addition, this chapter also raises a method of microemulsion extraction, in this method, the key skills also compose searching effective extract method besides the formula bolting. Once this method is determined, the process of extract is also the process of preparation, also, this method has a broad applicability, can lower the cost, enlarge the application scope of microemulsion drug delivery.2. The enact of quality standard of microemulsionThis chapter takes andrographolide mecroemulsion as example, reference emulsion and oral liquid quality standard in the Pharmacopoeia of the People's Republic of China, enact the correlated quality standard of microemulsion. The contents of protocol include name, prescription, method of preparation, characteristics, diagnosis, check, assaying, functions and indication, directions and dosage, specification, storage and expiration date. The check item includes the dose, relative density, PH value, dynamics check, assaying and microbial limit check. The draft account of the standard also includes the shape and particle diameter check of microemulsion.3. The comparative study of potency and bioavailability of Chinese herbal drug microemulsionThis chapter select andrographolide microemulsion, Rhizoma Chanxiong microemulsion, Herba Andrographitis Paniculatae microemulsion extract liquid as study object, researches the potency and bioavailability of microemulsion drug delivery from tree aspects which are active component,'whole'Chinese herb drug and microemulsion extract. In the experiments, three other dosage forms of the above-mentioned drug has been selected as comparative study, the findings display that microemulsion can enhance the potency and increase the bioavailability in different degree.4. The investigate of absorption mechanism of microemulsionThis chapter has select andrographolide microemulsion as example, utilize in situ perfusion model in rats to investigate the mechanism of absorption of microemulsion. In the experiment, inspect the influence of preparation factors (PH value, concentration) to absorption, the absorption information in stomach and different pare of intestine, the influence of carrier inhibitor, P-glycoprotein inhibitor, energy inhibitor to absorption. The experimental results display that, andrographolide microemulsion is absorbed well in stomach; it's absorption in intestine concerns with the drug's PH value, acidity drug is absorbed better than neutral and basis drug; the aborption of microemulsion show statuavility as the increase of the drug concentration; the best part to absorption is the middle and back end of intestine, one by one is ileum, jejunum, duodenum; the course of absorption needs carrier and is influenced by the excretion of P-glycoprotein, the absorption use no energy possibly; The absorption curve show obviously doublet. From the experimental results, it can be concluded that there are two main absorption pattern in the absorption course of microemulsion: the first one is passive transmembrane transport, this way exists both in stomach and intestine, it is absorbed well in stomach may be the main reason to show advanced absorption. Possibly because that microemulsion has a low surcace tension and small particle diameter, can easily transport the gastrointestinal tract epithelial cells, furthermore, in microemulsion system, the drug is packaged in milk drop, which can protect drug from the destroy of physical- chemistry factors and enzymatic in gastrointestinal tract; another absorption pattern is pinocytosised trough lymph, which mainly shown in the area where is full of PP, this may be the reason to show the second peak, is the important cause to raise the bioavailability of microemulsion.