Study On The Fu Ante Oral-nano Granular Formulation

Fu Ante, the pentacyclic triterpenes, is one of the main active ingredients in many Chinese medicines. It has anti-tumor, anti-diabetic, lipid-lowering, anti-inflammatory, antioxidant and other biological effects, particularly a significant effect at anti-tumor, anti-oxidation, anti-hepatitis, and it's expected to be a new anti-tumor, anti-hepatitis drug.Bioavailability was significantly reduced since Fu Ante is highly hydrophobic. Now it has been reported that Fu Ante Nano freeze-dried powder was used as liver targeting agents. We look forward to develope a solid nano oral formulations which is simple preparaed and easy to take to increase its clinical application.We have studied the Prescription, Technology, quality standards and stability of solid nano oral formulations.1. We found that a solid dispersion of Fu Ante can not be prepared with the traditional materials like PEG4000, PEG6000, PVP-k30 and so on. We added lipid, solid surface active agent to improve the dispersion of Fu Ante. Not only the extent but also the speed of dissolution of solid dispersion were increased significantly in water; the stripping solution was a nano-emulsion which has a long-term storage stability. The Orthogonal design was used to select the optimal prescription, and the result is: soybean lecithin 25%, Z-15 50%, Z-7 12.5%, PVP-k30 23%, Fu Ante 2%。2. We have studied the process of the preparation of solid dispersion, including solvent evaporated method, Freeze-drying method, and vacuum seasoning. The results showed the solvent evaporated method was the best considering on the state and dissolution results of the solid dispersions. So we choose the solvent evaporated method to prepare the complex solid dispersions.3. The quality analysis of Fu Ante nano oral preparation includes the character, identification, inspection, Content determination, etc. Content and dissolution was determined by HPLC. After the exploration of the chromatographic conditions and methodological validation, this method can accurately determine precise content of the sample. On this basis, the quality standards of the Fu Ante nano oral preparation were developed. While examining three batches of preparations, the indicators were in line with requirements, in vitro dissolution within 45min is more than 90%, showing a good immediate-release performance.4. Stability in the trial preparation, including: Impact Factors (temperature, humidity, light) and accelerated tests. After the high temperature and illumination test the Fu Ante oral-nano preparation (batch number 100123) had no significant changes in indicators, but after humidity test, the preparation showed significant changes in dissolution results. The preparations in high humidity conditions was instability, so we chose polyethylene materials as a packaging material which has low toxicity and good moisture resistance to ensure the storage stability of the preparation. Accelerated test results showed that the indicators are in line with requirements.The results showed that all the indicators of Fu Ante nano oral preparation are in line with requirements, The preparation released immediately in water and formed a nano-emulsion which could improve the bioavailability of Fu Ante and provide a new formulation for clinical application.