Chemical Reactivity of Aluminium-based Pharmaceutical Compounds used as Phosphate-binders

Abstract

Several aluminium-containing substances, including antacids used as phosphate-binders in treating renal failure, have been analysed in-vitro under different pH conditions for the release of Al3+ ions and for binding of phosphate. Control experiments on different forms of pure aluminium hydroxide validated the methods. At pH 2 it was the most amorphous forms which released Al3+ most rapidly. These aluminium ions, available for absorption by the patient, were released from all antacids tested, but no firm phosphate-binding was detected while the pH remained at 2. Phosphate was bound at pH 8, by adsorption onto the surface of aluminium hydroxide. No significant amounts of free Al3+ exist in solution at pH 8, since at that pH aluminium hydroxide is precipitated. The most amorphous forms of this solid were the most efficient phosphate-binders. Alumino-silicate salts require prior exposure to acid to produce free Al3+ before they can act as phosphate-binders, whereas amorphous aluminium hydroxide acts as an efficient phosphate-binder without prior exposure to acid. Chemical principles are employed to show why aluminium release and phosphate-binding are separate and independent processes. Methods are proposed for maximizing the activity of phosphate- binders in-vivo, while minimising aluminium release.

A Kinetic Study of Phosphate Adsorption by Boehmite

“…-V(∂C/∂t) ) AD p (∂c/∂r) r ) R (1) mass balance in particle: D p (∂ 2 c/∂ 2 r + (2/r)(∂c/∂r)) ) F A (∂q/∂t) (2) Freundlich isotherm:…”

“…1,2 However, aluminum hydroxide has low chemical stability against acid, dissolving completely in a solution of pH 3. An overload or long-term use of ALG results in the accumulation of aluminum in the body and has been considered a causative factor of such serious side effects as osteomalacia 3,4 or dialysis encephalopathy.…”

The evaluation of lanthanum trapped prussian blue as a phosphate binding agent with reduced bone uptake

“…It has been suggested that metal ion release from the drug and phosphate-binding takes place as an independent separate process, thus the phosphate binder should be designed to suppress the former activity, while boosting the latter. 6 Here we utilized this principle to enhance the high benefit/risk ratio by introducing a new lanthanum oral phosphate binder. The new drug is chemically formed by trapping lanthanum ions in the negatively-charged framework of colloidal Prussian blue (La@PB).…”