INFLUENCE OF PH ON IN-VITRO DISINTEGRATION OF PHOSPHATE BINDERS

Hyperphosphatemia, a common complication in patients with end-stage re nal disease, is treated with oral phosphate-binding medications that r estrict phosphorus absorption from the gastrointestinal (GI) tract. Im paired product performance, such as failure to disintegrate and/or dis solve in the Gr tract, could limit the efficacy of the phosphate binde r. 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 prod uct's performance. The purpose of this study was to determine the effe ct of pH on in vitro disintegration of phosphate binders. Fifteen diff erent commercially available phosphate binders (seven calcium carbonat e 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 teste d in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and s imulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate comple tely within 30 minutes. Results indicate that 9 of the 15 phosphate bi nders tested showed statistically significant differences in disintegr ation time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and inte stinal fluid were 80%, 80%, and 73%, respectively. The findings of thi s study show that the disintegration of commercially available phospha te binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how signif icantly this affects in vivo performance has yet to be studied. (C) 19 98 by the National Kidney Foundation, Inc.