目的：應(yīng)用藥物溶出／吸收仿生系統(tǒng)（drug dissolution / absorption simulating system, DDASS）研究丹酚酸B緩釋片的體外釋放規(guī)律，為中藥活性成分緩控釋制劑的設(shè)計(jì)提供新技術(shù)。方法：分別采用DDASS法和我國藥典收載的槳法對丹酚酸B固體制劑進(jìn)行體外釋放度試驗(yàn)，高效液相色譜法定量，SPSS軟件對累積釋放度進(jìn)行釋放模型擬合。改進(jìn)DDASS裝置使研究對象從藥物固體粉末或顆粒劑擴(kuò)展到片劑、膠囊劑等多種劑型，分別評價丹酚酸B緩釋片DDASS改進(jìn)前、后和槳法中釋放規(guī)律的相關(guān)性。結(jié)果：丹酚酸B原料藥及其緩釋片在改進(jìn)前DDASS模型中釋藥過程符合Weibull方程；而丹酚酸B緩釋片在改進(jìn)后DDASS模型中釋藥過程符合一級動力學(xué)方程，與槳法評價結(jié)果一致。DDASS改進(jìn)前、后與槳法釋藥規(guī)律相關(guān)性水平r值分別為0.788 4（r_{5, 0.05}＜r_前＜r_{5, 0.001}）和0.998 2（r_后＞r_{5, 0.001}）。結(jié)論：丹酚酸B緩釋片釋藥規(guī)律研究顯示改進(jìn)后DDASS法與槳法之間存在更為顯著相關(guān)性。較之槳法，DDASS法模擬了一個連續(xù)動態(tài)的、更接近人體消化道環(huán)境的釋藥過程，表明該法評價藥物固體制劑釋藥特性研究的合理性，為藥物劑型設(shè)計(jì)研究提供了新的技術(shù)平臺。

Objective: Drug dissolution and absorption simulating system (DDASS) was used to evaluate the release discipline of salvianolic acid B sustained-release tablets. It is anticipated to establish a new technology and method for studying the sustained-release or controlled-release preparations of Chinese herbal drugs active components. Methods: DDASS method and paddle method were used to study the release feature of salvianolic acid B sustained-release tablets. High performance liquid chromatography method was used to determine the concentration of salvianolic acid B. SPSS software will be used to fit curves. The applications are expanded to tablets and capsules from powder and granules by upgrading the DDASS method. The correlations between DDASS method and paddle method and between upgraded-DDASS method and paddle method were both evaluated. Results: The releasing curves of the salvianolic acid B crude drugs and sustained-release tablets both conformed to Weibull equation in the DDASS methods, while the release equation of the sustained-release tablets was first order kinetic equations in upgraded-DDASS method and paddle method, respectively. The correlation coeffient of the release features of DDASS method and the paddle method was 0.788 4 (r _5,0.05 < r_before < r _5,0.001), while the upgraded DDASS method and the paddle method was 0.998 2 (r_after > r_5,0.001). Conclusion: For salvianolic acid B sustained-release tablets, a good linear correlation is obtained between the cumulative dissolution rate in upgraded-DDASS method and the cumulative dissolution rate in the paddle method in the same length of time. Compared with paddle method, upgraded DDASS method simulates a continuous and dynamic drug- releasing course which is closer to course of drugs being transported through the gastrointestinal tract. The result confirms the reasonableness of upgraded DDASS method to assess the releasing features of solid preparations and establish a new technology platform for the study of devising drug preparations.

長江學(xué)者和創(chuàng)新團(tuán)隊(duì)發(fā)展計(jì)劃；“重大新藥創(chuàng)制”科技重大專項(xiàng)（2009ZX09304-002）；國家自然科學(xué)基金項(xiàng)目（30772778）；國際科技合作計(jì)劃項(xiàng)目（2007DFC31670）