Stewart A G, Grant D J, Newton J M
J Pharm Pharmacol. 1979 Jan;31(1):1-6. doi: 10.1111/j.2042-7158.1979.tb13410.x.
The in vitro release of a model low dose drug, riboflavine, from hard gelatin capsules, formulated with a range of diluents, in the absence and presence of magnesium stearate (0.5, 1.0 and 2.0% w/w), has been assessed by a dissolution technique. Comparison of the values of the time for 50% of the drug content of the capsule to appear in solution T50, by analysis of variance, indicated that the type of diluent significantly influenced the drug release. Irrespective of the magnesium stearate content, the diluents could be ranked in the following order of effectiveness: Primojel greater than sodium bicarbonate greater than Avicel congruent to Dri-flo starch congruent to lactose greater than Emcompress congruent to kaolin greater than starch. Correction of the T50 values for possible adsorption of riboflavine onto the water insoluble diluents, using experimentally determined adsorption isotherms, altered the relative order of effectiveness of the diluents to Primojel greater than sodium bicarbonate greater than kaolin congruent to lactose greater than Avicel congruent to Dri-flo starch greater than Emcompress greater than starch. Comparison of the urinary excretion of riboflavine, after administration of capsule formulations containing lactose, Emcompress or kaolin as the diluent, to volunteers, suggests that the dissolution results not corrected for adsorption provide a better indication of the in vivo performance of the formulations.
采用溶出技术评估了一种低剂量模型药物核黄素在硬明胶胶囊中的体外释放情况，该胶囊用一系列稀释剂配制，且在有和没有硬脂酸镁（0.5%、1.0%和2.0% w/w）的情况下进行。通过方差分析比较胶囊中50%药物含量出现在溶液中的时间（T50）值，结果表明稀释剂类型对药物释放有显著影响。无论硬脂酸镁含量如何，稀释剂的有效性可按以下顺序排列：预胶化淀粉大于碳酸氢钠大于微晶纤维素等同于无水磷酸氢钙淀粉等同于乳糖大于埃姆普雷斯等同于高岭土大于淀粉。利用实验测定的吸附等温线，对核黄素可能吸附到水不溶性稀释剂上的情况校正T50值后，稀释剂的相对有效性顺序变为：预胶化淀粉大于碳酸氢钠大于高岭土等同于乳糖大于微晶纤维素等同于无水磷酸氢钙淀粉大于埃姆普雷斯大于淀粉。给志愿者服用含有乳糖、埃姆普雷斯或高岭土作为稀释剂的胶囊制剂后，比较核黄素的尿排泄情况，结果表明未校正吸附的溶出结果能更好地反映制剂的体内性能。
