Eudragit和腸溶性高分子組成比例對nicardipine溶離釋出之影響   全文下載

The Effect of Eudragit and Enteric Polymer Composite on the Release of Nicardipine

本研究以溶媒蒸發法來製備具有持續釋放效果之Nicardipine固體分散系；以溶離試驗來測定藥物在模擬胃液（pH 1.2）和磷酸緩衝溶液（pH 6.8）中之釋出曲線圖並與市售長效製劑PerdipineR作比較。結果顯示配方中Nicardipine/Eudragit RS（N/RS）比例小於1/5時即具有持續釋出之效果。比較實驗配方N/RS = 1/5和市售售製劑PerdipineR在模擬胃液和磷酸緩衝溶液中之溶離曲線，結果顯示實驗配方在模擬胃液中之溶出速率較市售品為快，但在磷酸緩衝溶液中之溶出速率則較為緩慢。為了製得具有與Perdipine相似作用之持續釋出配方，添加腸溶性高分子如HPMCAS-LF（HPMCAS）和HPMCP-55（HPMCP）於配方當作coplymer以增加藥物在磷酸緩衝溶液中之溶出速率，結果顯示含有腸溶性高分子20-40%時，可增加藥物的溶離效率達2.35-20倍。其中實驗配方N/RS/HPMCP = 1/3.5/1.5在磷酸緩衝溶液和模擬胃液中之溶離曲線和PerdipineR相似（f2值大於50），顯示合併使用Eudragit RS和腸溶性高分子可製得具有持續釋放效果之Nicardipine固體分散系。

The purpose of this study was to investigate the sustained release of nicardipine/polymer solid dispersions prepared by solvent evaporation method. The release pattern of drug from solid dispersions was evaluated by the dissolution test in both dissolution medium of phosphate buffer pH 6.8 or gastric acid fluid pH 1.2, and was compared with a commercial long acting product Perdipine®. The results showed that the formulations with lower ratio of Nicardipine/Eudragit RS (N/RS) (below 1/5) had sustained release effect in gastric acid fluid (pH 1.2). The release rate of formulation of N/RS = 1/5 was slightly faster than that of Perdipine® in gastric acid fluid in the early stage. On the contrary, the release rate was lower than that of Perdipine® in phosphate buffer (pH 6.8). The enteric polymers such as HPMCAS-LF grade (HPMCAS) and hydroxypropyl methylcellulose phthalate, HP-55 grade (HPMCP) were incorporated into the formulation of NC/ERS = 1/5 solid dispersion to improve the drug release in both dissolution medium. It was found that the dissolution efficiencies of drug were increased 2.35-21.08 folds with the addition of 20-40% of enteric polymer in pH 6.8 media. Among these formulations of N/RS/HPMCP = 1/3.5/1.5 had similar dissolution pattern with Perdipine® in either medium of phosphate buffer or gastric acid fluid ( f2 values were above 50), showing that the sustained release dosage form of nicardipine solid dispersions could be developed by using the combination of Eudragit RS and enteric polymer.