Division of Product Quality Research, Office of Pharmaceutical Science, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
J Pharm Sci. 2013 Apr;102(4):1370-81. doi: 10.1002/jps.23454. Epub 2013 Jan 18.
The aims of this study were to systematically evaluate the effects of pH levels, phosphate concentrations, and tablet integrity on the phosphate binding profiles of lanthanum carbonate chewable tablets, and to compare the in vitro phosphate binding efficacy of one reference and two test products of lanthanum carbonate chewable tablets. Langmuir equation was utilized to calculate the binding constants k1 and k2 . The phosphate binding to the tablets of lanthanum carbonate product was pH dependent, with a faster binding rate at low pH. The crushed tablets bind phosphate more rapid. Compared with the whole tablets, the kinetic binding profiles from the crushed tablets were less variable under all conditions for both test and reference products. The phosphate level has a significant impact on the phosphate binding for both whole and crushed tablets under all pH conditions, with more binding at higher phosphate concentration. The phosphate binding profiles displayed significant difference among the products. For a crushed tablet, the phosphate binding to lanthanum reached equilibrium within 8 h under all conditions. The 90% confidence interval for the k2 ratio (test/reference) was well within the 80%-125% under all pH conditions. However, the k1 ratio varies from 54% to 144%. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1370-1381, 2013.
本研究的目的是系统地评估 pH 值、磷酸盐浓度和片剂完整性对碳酸镧咀嚼片的磷酸盐结合特性的影响,并比较一种参考品和两种碳酸镧咀嚼片的测试品的体外磷酸盐结合效果。利用 Langmuir 方程计算结合常数 k1 和 k2。碳酸镧咀嚼片的磷酸盐结合与 pH 值有关,在低 pH 值下具有更快的结合速率。破碎的片剂比完整的片剂更快地结合磷酸盐。与完整片剂相比,在所有条件下,测试品和参考品的破碎片剂的动力学结合曲线的变异性更小。在所有 pH 值条件下,磷酸盐水平对完整和破碎片剂的磷酸盐结合都有显著影响,磷酸盐浓度越高,结合越多。各产品的磷酸盐结合特性有显著差异。对于破碎的片剂,在所有条件下,磷酸盐与镧在 8 小时内达到平衡。在所有 pH 值条件下,k2 比值(测试品/参考品)的 90%置信区间均在 80%-125%范围内。然而,k1 比值从 54%到 144%不等。©2013Wiley Periodicals, Inc. 和美国药剂师协会 J Pharm Sci 102:1370-1381, 2013。