Hosny E A, el-Mahrouk G M, Gouda M W
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Drug Dev Ind Pharm. 1998 Jul;24(7):661-6. doi: 10.3109/03639049809082368.
Diclofenac sodium enteric-coated beads were prepared using the conventional pan coating technique. Eudragit L100 was used as a pH-dependent release-controlling polymer. The beads were evaluated for their particle size distribution, drug loading efficiency, flowability, in vitro release in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8), and bioavailability in beagle dogs relative to the commercial enteric-coated tablets Voltaren. The beads showed a narrow particle size distribution in which 83% of the beads were in the range of 1-2 mm. The actual yield of the beads was 90.5% and their drug loading was 92%. The beads released about 8% of the drug during 2 hr of dissolution in 0.1 N HCl, and the commercial tablets released no drug. In phosphate buffer (pH 6.8) both formulations released their drug content in 1 hr. Both formulations are, therefore, in compliance with the USP requirements for release from enteric-coated dosage forms. The in vivo availability study in six beagle dogs revealed that the formulated enteric-coated beads filled in hard gelatin capsules had a 197.54% bioavailability relative to that of the commercial Voltaren tablets. The tablets showed a significantly lower (p < 0.05) area under curve for 0-8 hr (AUC0-8 hr) of 13.44 +/- 15.02 micrograms hr/ml compared to 26.55 +/- 5.19 micrograms hr/ml for the capsules. The capsules showed a nonsignificantly (p > 0.05) higher peak plasma concentration (Cmax) of 6.77 +/- 0.67 micrograms/ml compared to 5.88 +/- 7.38 micrograms/ml for the tablets. The time to reach peak (Tmax) values were 2 +/- 1.48 and 2.25 +/- 1.08 hr for the capsules and tablets, respectively. The capsules showed less interdog variability with respect to Cmax (CV% 34.6) and AUC (CV% 19.55) compared to CV% 79.9 and 111.76, respectively, for the commercial tablets.
采用常规锅包衣技术制备双氯芬酸钠肠溶包衣微丸。用Eudragit L100作为pH依赖型控释聚合物。对微丸进行了粒度分布、载药效率、流动性、在0.1N盐酸（pH 1.2）和磷酸盐缓冲液（pH 6.8）中的体外释放以及相对于市售肠溶衣片扶他林在比格犬体内的生物利用度评价。微丸呈现窄粒度分布，其中83%的微丸粒径在1 - 2mm范围内。微丸的实际收率为90.5%，载药量为92%。微丸在0.1N盐酸中溶解2小时期间释放约8%的药物，而市售片剂未释放药物。在磷酸盐缓冲液（pH 6.8）中，两种制剂均在1小时内释放其药物含量。因此，两种制剂均符合美国药典对肠溶剂型释放的要求。对6只比格犬进行的体内生物利用度研究表明，填充于硬明胶胶囊中的制剂肠溶包衣微丸相对于市售扶他林片剂的生物利用度为197.54%。片剂在0 - 8小时的曲线下面积（AUC0 - 8 hr）显著更低（p < 0.05），为13.44±15.02微克·小时/毫升，而胶囊为26.55±5.19微克·小时/毫升。胶囊的血浆峰浓度（Cmax）略高（p > 0.05），为6.77±0.67微克/毫升，而片剂为5.88±7.38微克/毫升。胶囊和片剂达到峰浓度的时间（Tmax）值分别为2±1.48小时和2.25±1.08小时。与市售片剂的Cmax变异系数（CV% 79.9）和AUC变异系数（CV% 111.76）相比，胶囊在Cmax（CV% 34.6）和AUC（CV% 19.55）方面显示出较小的犬间变异性。
