Study On Liquid-solid Compressed Tablets Of Supersaturated Self-microemulsion Of Andrographolide

Andrographolide is derived from the traditional Chinese medicine Andrographis paniculata.It has a good effect on the upper respiratory tract and diarrhea caused by the virus and virus.It has extensive pharmacological activity and has the beauty of natural antibiotics.The chemical structure of andrographolide is two terpene lactone,which is almost insoluble in water(about 0.072mg/mL),which leads to low absorption after oral administration,and the clinical application is greatly limited.The study shows that the self microemulsification system(SMEDDS)is suitable for class II and class IV lipids soluble or poor water-soluble drugs.The solubilization of drugs can be increased by reducing the size of the drug particle size and the formation of micelles and other methods.The supersaturated self microemulsification system(S-SMEDDS)can avoid the precipitation of SMEDDS gastrointestinal tract.Crystallization further increases the stability and effectiveness of the preparation.In order to make the S-SMEDDS solid to facilitate the storage and carrying of the patient,it is combined with the liquid-solid compression technology to increase the stability of the preparation and play the role of solubilization.The aim of this study is to enhance the solubility of Andrographolide by combining two drug delivery systems.First of all,before the prescription,the TLC identification of andrographolide was carried out.At the same time,the content of andrographolide was determined by HPLC method,and the best dissolution method was selected to lay the foundation for the screening and quality evaluation of the following formulation.By testing the solubility and compatibility of andrographolide in the various auxiliary materials,the optimum three-phase was selected as oil phase: EO,surfactant: Tween-80,surface active agent: PEG400;and then the pseudo three element phase diagram was drawn to determine the approximate ratio of three phases: EO:10%~40%,tween-80: 30%~80%,PEG400:20%~80%,finally,The average particle size,emulsification time and PDI were the best indexes,and the optimum prescription was optimized by simplex method.Finally,the best supersaturation inhibitor was selected by the analysis of crystallization,particle size,polydispersity index,emulsification time and the dissolution of andrographolide.The best supersaturated self microemulsion formulation was: ethyl oleate-(polysorbate-80)-polyethylene glycol 400-hydroxypropyl methyl cellulose K4M(20:35:45:1).On the basis of supersaturated self microemulsifying drug release system,the liquid solid compression technology was used to solidify it and combine the two advantages to construct a solid compressing powder system with good fluidity and compressibility.Firstly,the carrier material and coating material were selected with the retention value of solid adsorbed liquid,and then according to the Spireas mathematical model and liquid solid compression technology,the dosage of carrier material and coating material,the ratio of drug liquid and R value were selected by the evaluation of powder fluidity and dissolution.The final prescription is: liquid load factor: 0.1690,R=20,liquid ratio: 25%,andrographolide raw material: 10 mg,blank supersaturated self microemulsion: 40 mg,MCC PH302:236.69 mg,Sylysia:11.83 mg,CMS-Na:14.93 mg,tablet weight 313.45 mg.The properties of the supersaturated self microemulsion solid compression system were investigated step by step,and the advantages of the combination of the supersaturated self microemulsion system and the liquid solid compression system were explored,and the principle of solubilization was preliminarily analyzed and explored.The results show that the emulsified particle size of the supersaturated self microemulsification system is small(29.26±0.56),the time is short(63.39 ±2.03),and the dispersion is even(0.191± 0.02).It has the advantage of liquid excipient in the liquid solid compress.The flow performance and the compressibility of the over saturated self microemulsion are good,the wettability is good,and the powder differential scanning is scanned.Thermal analysis also showed that drugs existed in the molecular or amorphous state in the system,thereby increasing the dissolution of drugs.Finally,the redispersibility of the supersaturated self microemulsion solid compress sheet shows that it has the characteristics of microemulsion particle size(56.3± 0.57)nm and dispersion(0.195±0.039),and the reproducibility of dissolution(RSD 5%)is good,which indicates that the preparation process is stable,and the high dissolution body is the advantage of the two combined applications.Finally,the properties,identification,tablet examination and critical relative humidity of andrographolide self microemulsion solid compacted tablets were investigated,and the HPLC method was established for the determination of andrographolide content.The results of the preliminary quality evaluation were in line with the Pharmacopoeia regulations.A preliminary investigation of its stability indicates that the product should be kept at low temperature and moisture proof.