Li S P, Felt R G, Di Paolo L C, Huang M Y, Williams R O
Rhone-Poulenc Rorer Pharmaceuticals Inc., Fort Washington 19034, USA.
Pharm Res. 1995 Sep;12(9):1338-42. doi: 10.1023/a:1016229808716.
To develop and evaluate the in vitro/in vivo performance of diltiazem sustained release pellets that were prepared by the Wurster column process.
Pellets containing diltiazem were prepared by spraying a slurry of micronized diltiazem hydrochloride, pharmaceutical glaze and alcohol onto an appropriate mesh fraction of nonpareil seeds using the Wurster column. A two-step drug layering process was used to increase drug loading from 60% to 75%. The oven-dried diltiazem basic pellets were coated with ethylcellulose/dibutyl sebacate coating solution to yield diltiazem sustained release pellets. An open, randomized Latin square, three-way crossover clinical study was used to evaluate the in vivo performance of the coated product.
Altering the mesh fraction of the starting nonpareil seeds for this layering process was found to affect the release characteristics of drug from the pellets. An oven-drying step was required to stabilize the diltiazem basic pellets. The thicker the drug loading layer the longer the oven drying is needed to stabilize the pellets. The diltiazem sustained release pellets produced by these methods displayed sustained release dissolution profiles both in vitro and in vivo. Diltiazem basic pellets coated with a 0.6% ethylcellulose/dibutyl sebacate coating showed a different rate of absorption (lower Cmax and higher Tmax) and the same extent of absorption as compared to Cardizem tablets.
Clinical data confirmed that this formulation approach is an effective means to produce a diltiazem sustained release product.
研发并评估采用Wurster柱法制备的地尔硫䓬缓释微丸的体外/体内性能。
使用Wurster柱，将微粉化盐酸地尔硫䓬、药用包衣材料和乙醇的混悬液喷雾于适当目数的小丸种子上，制备含地尔硫䓬的微丸。采用两步法药物层积工艺将载药量从60%提高至75%。将经烘箱干燥的地尔硫䓬素丸用乙基纤维素/癸二酸二丁酯包衣液包衣，制得地尔硫䓬缓释微丸。采用开放、随机拉丁方、三交叉临床研究评估包衣产品的体内性能。
发现改变该层积工艺起始小丸种子的目数会影响微丸中药物的释放特性。需要进行烘箱干燥步骤以稳定地尔硫䓬素丸。载药层越厚，稳定微丸所需的烘箱干燥时间越长。通过这些方法制备的地尔硫䓬缓释微丸在体外和体内均呈现缓释溶出曲线。与硫氮䓬酮片相比，用0.6%乙基纤维素/癸二酸二丁酯包衣的地尔硫䓬素丸显示出不同的吸收速率（较低的Cmax和较高的Tmax）和相同的吸收程度。
临床数据证实，这种制剂方法是生产地尔硫䓬缓释产品的有效手段。
