Formulation and in vitro and in vivo availability of diclofenac sodium enteric-coated beads

被引:26
作者
Hosny, EA [1 ]
El-Mahrouk, GM [1 ]
Gouda, MW [1 ]
机构
[1] King Saud Univ, Coll Pharm, Dept Pharmaceut, Riyadh 11451, Saudi Arabia
关键词
D O I
10.3109/03639049809082368
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Diclofenac sodium enteric-coated beads were prepared using the conventional pan coating technique. Eudragit L-100 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 I 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 (AUC(0-8 hr)) of 13.44 +/- 15.02 mu g hr/ml compared to 26.55 +/- 5.19 mu g hr/ml for the capsules. The capsules showed a nonsignificantly (p > 0.05) higher peak plasma concentration (C-max) of 6.77 +/- 0. 67 mu g/ml compared to 5.88 +/- 7.38 mu g/ml for the tablets. The time to reach peak (T-max) 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 C-max (CV% 34.6) and AUC (CV% 19.55) compared to CV% 79.9 and 111. 76 respectively, for the commercial tablets.
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收藏
页码:661 / 666
页数:6
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