Objective: To prepare glycyrrhizin acid phospholipids-bile salts mixed micelles

and optimize its formulation by central composite design-response surface methodology. Method: Glycyrrhizin acid phospholipids-bile salts mixed micelles was prepared by film dispersion method

solubilization of bile salts to phospholipids was investigated by single factor test

solubility of phospholipids in bile salt solution was determined.The molar concentration of bile salts and pH of buffered saline solution were selected as investigation factors

with solubility of glycyrrhizin acid and drug loading of mixed micelles as indexes

formulation was optimized by central composite design test

and fitted by multiple linear and binomial nonlinear equation

then optimum precription ratio was determined by response surface methodology. Result: The best prescription was as following:phospholipids-bile salts 1.19: 1

pH of buffered saline solution 7.4

the molar concentration of bile salts 15 mmol·L-1;Solubility of glycyrrhizin acid 21.12 g·L-1

drug loading of mixed micelles was 53.93%;There was a little deviation between the theoretic value and the measured value

it showed that this model had a good prediction. Conclusion: The solubility of glycyrrhizin acid could significantly increase by preparing bile salts-phospholipids micelles

and this optimized technology was simple and stable.