RESUMO
Objective: To optimize the preparation of Saussureae Involucratae Herba extract (SIHE)-composite phospholipid liposome (CPL) by the central composite design-response surface methodology (CCD-RSM) and to investigate the in vitro release of drugs. Methods: The method of ammonium sulfate transmembrane gradients was adopted to prepare SIHE-CPL. The single factor experiments were used for the key experimental factors and their test ranges. Based on the single factor experiments, with the size of SIHE-CPL, polymey disperse index (PDI), encapsulation efficiency (EE), and Zeta potential as dependent variables, central composite design was adopted to optimize the preparation technology by taking the content of phospholipid and the content of cholesterol as independent variables, test results were fitted by multiple linear and binomial nonlinear equations, and optimum formulation was selected by RSM, then the in vitro release behavior of the drug was studied by method of dynamic dialysis. Infrared (IR) spectroscopy and X-ray diffraction (XRD) pattern were used to analyze the spectroscopic properties of SIHE-CPL. Results: The second-order polynomial equation was superior to the linear one, the observed values agreed well with model predicted values. The optimal process conditions were as follows: Size of SIHE-CPL was (102.7 ± 5.1) nm, PDI was 0.154 ± 0.017, EE of chologenic acid and rutin was (87.68 ± 2.57)% and (84.18 ± 2.97)%, Zeta potential was (-28.4 ± 2.2) mV, SIHE-CPL and solution of SIHE were both accorded with the first order model, and IR analysis and XRD proved the formation of SIHE-CPL. Conclusion: The size and PDI of SIHE-CPL are low, the EE and Zeta potential of SIHE-CPL are high. CCD-RSM could be successfully used to optimize the prescription of SIHE-CPL.
RESUMO
Objective: To optimize the preparation of Saussureae Involucratae Herba extract (SIHE) phospholipid complex (PC) by the central composite design-response surface method, and to increase the bioavailability of SIHE. Methods: Five main factors including reaction solvent, reaction time, SIHE concentration, reaction temperature, and ratio of reactants on this reaction were investigated. On the basis of single factor test, central composite design was further adopted to arrange experiments in search of a curve fitting model between factors and effects. The optimal formulation was predicted by response surface method and was verified as well. The structure of SIHE-PC was analyzed by infrared spectroscopic (IR) analysis and X-ray diffraction (XRD). Results: The correlation coefficient of second-order quadratic model was high. The optimal process conditions were as follows: The ratio of SIHE and soybean lecithin was 1∶2.5, reaction concentration was 10 mg/mL, reaction time was 2 h, chologenic acid complex molar ratio was 96%, and rutin complex molar ratio was 93%. IR analysis and XRD proved the formation of SIHE-PC. Conclusion: Central composite design-response surface method is successfully used for the optimization on preparation of SIHE-PC, with good predictability and stability.