目的 星點設(shè)計-效應(yīng)面法優(yōu)化阿德福韋包合物的制備工藝.方法 以飽和水溶液法制備阿德福韋-β-環(huán)糊精包合物,采用星點設(shè)計優(yōu)化制備工藝,以β-環(huán)糊精與阿德福韋的投料配比、包合時間、包合溫度為自變量,包合率、收率為因變量,分別進行多元線性回歸和二項式方程擬合,依據(jù)最佳數(shù)學模型描繪效應(yīng)面選擇最佳處方工藝進行驗證試驗.結(jié)果 二項式方程擬合度較高,預(yù)測性好,相關(guān)系數(shù)r=0.965;效應(yīng)面法優(yōu)選出的最佳工藝為：β-環(huán)糊精與阿德福韋的投料配比約為3:1,包合時間為5 h,包合溫度為60 ℃.最佳工藝驗證試驗結(jié)果與二項式擬合方程預(yù)測值偏差為(1.31±0.69)%.結(jié)論 應(yīng)用星點設(shè)計-效應(yīng)面優(yōu)化法能夠精確有效地優(yōu)化阿德福韋-β-環(huán)糊精包合物的制備工藝,優(yōu)選出的最佳工藝穩(wěn)定可行,可用于工業(yè)生產(chǎn).

Objective To optimize the preparation technology of adefovir-β-cyclodextrin inclusion complex by central composite design and response surface methodology. Methods Saturated aqueous solution method was used to prepare adefovir-β-cyclodextrin inclusion complex. The preparation was optimized by central composite design. With β-cyclodextrin/adefovir, inclusion time, and temperature as the independent variables, and with the inclusion rate and yield as the dependent variable, the binomial and linear equations were fitted to the data of overall desirabilities, and the resulting equation was used to produce 3-D response surface graphs, through which optimal formulation was predicted, and the best prescription process was chosen to verity test. Results The fitting of second-order quadratic model was high, and the correlation coefficient was 0.965. The optimum conditions for the preparation of adefovir-β-cyclodextrin inclusion complex were as follows: β-cyclodextrin/adefovir of 3:1, inclusion time of 5 h, and inclusion temperature at 60 ℃. The deviation between the result of best craft verification test and the binomial fitting equation forecast value was (1.31 ± 0.69)%. Conclusion Central composite design and response surface methodology is successfully used to optimize the preparation technology of adefovir-β-cyclodextrin inclusion complex. The optimized process is reliable, stable, and available for the industrial production.

國家重點基礎(chǔ)研究發(fā)展計劃(973計劃)項目(2010CB735600)