Preparation Of Solid Dispersion System Of Baicalin Phospholipid Complex And Study On Its Oral Bioavailability

Baicalin is the main active component in the dried roots of Scutellaria baicalensis Georgi.With anti-inflammatory,anti-virus,anti-oxidation,anti-tumor and cardiovascular diseases and other pharmacological effects.In recent years,the treatment of tumors by traditional Chinese medicine has become a trend.Baicalin has a low toxicity and a wide range of anti-tumor effects,so it has a good development prospect in tumor treatment.However,baicalin has poor water solubility and fat solubility,easy oxidation,poor absorption in vivo and low bioavailability,which limits the development and clinical application of baicalin.The solid dispersion of baicalin phospholipid complex was prepared to increase the dissolution and absorption of the drug.The preparation conditions of baicalin phospholipid complex and solid dispersion system were screened and characterized.In vivo pharmacokinetic studies were conducted on rats to compare the bioavailability of baicalin API,baicalin phospholipid complex and baicalin phospholipid complex solid dispersions.The specific contents are as follows:1.Preparation and optimization of baicalin phospholipid complex.Baicalin phospholipid complex was prepared by solvent method.The compound rate was used as the evaluation index.The preparation process of baicalin phospholipid complex was optimized by designing a four-factor and three-level orthogonal test,which took the compound rate and the baicalin mass fraction in the complex as the indexes for comprehensive scoring.The optimal preparation method was determined as follows:tetrahydrofuran as the reaction solvent,baicalin and lecithin feeding ratio 1:3,concentration of 2.5mg/mL,reaction at 50?for 1 hour.The compound rate was 94.42%,the mass fraction of baicalin was 22.50%,and the process conditions were stable and feasible.2.Preparation of solid dispersion of baicalin phospholipid complex.The solid dispersion of baicalin phospholipid complex was prepared by solvent method,and the carrier types?PVPk30,PEG6000 and poloxam 188?and carrier proportions?1:0.5,1:1,1:1.5 and 1:2?were screened by single factor test with dissolution degree as the index.The best proportion was determined when PVP30 was the best carrier and the ratio of baicalin phospholipid complex to carrier was 1:2.The baicalin mass fraction of the solid dispersion of baicalin phospholipid complex was 7.55%and the cumulative dissolution was 92.19%.3.Characterization of solid dispersion of baicalin phospholipid complex.TLC showed that the solid dispersion of baicalein,baicalein phospholipid complex and baicalein phospholipid complex were spotted at the same location.The uv spectrum analysis results showed that the uv absorption peak of baicalin did not change before and after the preparation of baicalin phospholipid complex solid dispersion,indicating that no new compounds were generated during the preparation process.The results of scanning electron microscopy?SEM?showed that the crystal structure of baicalin disappeared in the solid dispersion of baicalin phospholipid complex and baicalin phospholipid complex.Infrared spectroscopy?IR?analysis showed that no new bonds were formed in the solid dispersion of baicalin phospholipid complex,nor was it a simple physical mixture.4.Preliminary study on the stability of baicalin phospholipid complex solid dispersion.High temperature test,high humidity test,strong light test and long-term retention test were carried out to preliminarily evaluate the stability of baicalin phospholipid complex solid dispersion.The results of high temperature,high humidity and strong light test showed that the solid dispersion of baicalin phospholipid complex was unstable under high temperature and strong light.The content of baicalin did not decrease significantly after 10 days of treatment under high humidity,but the moisture absorption clumped.The results showed that the solid dispersion of baicalin phospholipid complex should be kept under low temperature and dry condition.The long-term retention test results showed that the solid dispersion of baicalin phospholipid complex was placed at room temperature,dry and dark for 6 months,the color appearance did not change significantly,and the content of baicalin did not decrease significantly within 3 months,indicating that it was relatively stable under this condition.5.Study on oral bioavailability of solid dispersion of baicalin phospholipid complex.The SD rats were given baicalin,baicalin phospholipid complex and its solid dispersion by gavage respectively,and the dose was 70 mg·kg^-1.The blood concentration of baicalin was determined by HPLC,the drug-time curve was drawn,and pharmacokinetic parameters were calculated by DAS2.0.The average peak concentration C_max of the solid dispersion of baicalin phospholipid complex was 2.707 g·mL^-1,which was statistically significant compared with the C_max of 0.745 g·mL^-1 of baicalin API and the C_max of 2.219g·mL^-1 of phospholipid complex?P<0.05 or P<0.01?.Compared with AUC_0-t7.673 g·h·mL^-1 of baicalin phospholipid complex and AUC_0-t 21.188 g·h·mL^-1of baicalin API and AUC_0-t-t 7.673 g·h·mL^-1 of phospholipid complex in the solid dispersion group,the differences were statistically significant?P<0.05 or P<0.01?.The results showed that the preparation of baicalin phospholipid complex into solid dispersion could further improve the bioavailability of baicalin.