往復(fù)筒法測定雙氯芬酸鈉緩釋片釋放度的基本特征及其體外釋放行為評價

Basic Characteristics and in vitro Dissolution Behavior Evaluation of Diclofenac Sodium Sustained-release Tablets Determined by Reciprocating Cylinder

探索往復(fù)筒法測定雙氯芬酸鈉緩釋片釋放度的基本特征，建立往復(fù)筒法測定釋放度檢查方法，比較不同企業(yè)雙氯芬酸鈉緩釋片體外釋放曲線，評價其體外釋放行為。

采用往復(fù)筒溶出儀，往復(fù)頻率為10dips/min，上篩網(wǎng)目數(shù)為20目，下篩網(wǎng)目數(shù)為40目，停留時間為10s，滴水時間為60s，模擬人體胃腸道序貫性pH生理環(huán)境，經(jīng)pH1.2鹽酸溶液中釋放2h后，再在pH4.5醋酸鹽緩沖液中釋放1h，最終在pH6.8磷酸鹽緩沖液中釋放 20h，對9家生產(chǎn)企業(yè)市售的雙氯芬酸鈉緩釋片進(jìn)行體外釋放試驗，在規(guī)定時間點取樣后采用高效液相色譜法（HPLC）測定雙氯芬酸鈉緩釋片的溶出量，繪制體外釋放曲線?？疾觳煌尫艞l件對體外釋放行為的影響；對體外釋放曲線進(jìn)行模型擬合，考察其釋放動力學(xué)及釋藥機(jī)制；同時通過計算相似因子（f2）評價其釋放曲線相似性，評價體外釋放行為。

A reciprocating cylinder dissolution instrument was used with a reciprocating frequency of 10 dips/min; the mesh number of the upper sieve was 20; the mesh number of the lower sieve was 40; the residence time was 10s, and the drip time was 60s, which simulated the sequential pH physiological environment of the human gastrointestinal tract. After being released in pH1.2 hydrochloric acid solution for 2h, then released in pH4.5 acetate buffer for 1h, and finally released in pH6.8 phosphate buffer for 20h, the in vitro release test of diclofenac sodium sustained-release tablet commercially available in 9 manufacturers was carried out, and the dissolution amount of diclofenac sodium sustained-release tablet was determined by HPLC method after sampling at the specified time point, and the in vitro dissolution curve was drawn. To investigate the effects of different release conditions on in vitro dissolution behavior; The model fitting of the in vitro dissolution curve was carried out to investigate its release kinetics and drug release mechanism. At the same time, the similarity of the dissolution curve was evaluated by calculating the similarity factor (f2), so then the dissolution behaviors in vitro were evaluated. 

生產(chǎn)企業(yè)A、B、D和F的雙氯芬 酸鈉緩釋片體外釋放曲線與參比制劑相似，其他生產(chǎn)企業(yè)均不相似；除生產(chǎn)企業(yè)G外，其他生產(chǎn)企業(yè)的雙氯芬酸鈉緩釋片體外釋放曲線以一級釋放為最佳擬合模型；生產(chǎn)企業(yè)G的釋放機(jī)制為Ⅱ相轉(zhuǎn)運(yùn)，其他生產(chǎn)企業(yè)的釋放機(jī)制均為藥物擴(kuò)散和骨架溶蝕共同作用。

該方法可為雙氯芬酸鈉緩釋片研發(fā)及質(zhì)量一致性評價提供參考，也為往復(fù)筒法在緩控釋制劑中的應(yīng)用提供思路。

雙氯芬酸鈉緩釋片；往復(fù)筒法；釋放曲線；相似因子；釋藥機(jī)制

往復(fù)筒法測定雙氯芬酸鈉緩釋片釋放度的基本特征及其體外釋放行為評價.pdf