Stamatakis M K, Alderman J M, Meyer-Stout P J
West Virginia University, Morgantown 26506-9520, USA.
Am J Kidney Dis. 1998 Nov;32(5):808-12. doi: 10.1016/s0272-6386(98)70137-4.
Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.
高磷血症是终末期肾病患者的常见并发症，可通过口服磷结合药物进行治疗，这类药物可限制胃肠道对磷的吸收。产品性能受损，如在胃肠道中无法崩解和/或溶解，可能会限制磷结合剂的疗效。对于局部作用于胃肠道的药物（如磷结合剂），崩解对于预测体外产品性能可能与溶解同样重要。此外，终末期肾病患者的胃肠道pH值范围较广，而pH值会影响产品性能。本研究的目的是确定pH值对磷结合剂体外崩解的影响。使用美国药典（USP）标准崩解仪对15种不同的市售磷结合剂（7种碳酸钙片剂剂型、2种醋酸钙片剂剂型、3种氢氧化铝胶囊剂型和3种氢氧化铝片剂剂型）进行了研究。磷结合剂在模拟胃液（pH 1.5）、蒸馏水（pH 5.1）和模拟肠液（pH 7.5）中进行测试。产品不合格定义为两片或更多片个体片剂或胶囊在30分钟内未完全崩解。结果表明，在测试的15种磷结合剂中，有9种在基于pH值的崩解时间（DT）上显示出统计学上的显著差异。在蒸馏水、胃液和肠液中通过崩解研究测试的结合剂百分比分别为80%、80%和73%。本研究结果表明，市售磷结合剂的崩解具有高度变异性。pH值对大多数测试的磷结合剂的体外崩解有显著影响；其对体内性能的影响程度还有待研究。
