Ammonium inhibition of the intercalation of dicarboxylic acid molecules into octacalcium phosphate layer by substitution

Octacalcium phosphate (OCP) is an attractive material for becoming the centerpiece of medical combination products as a layered calcium phosphate because it exhibits excellent biocompatibility and because various molecules can be intercalated between its layers. However, the factors that govern various events, such as molecular substitution into an OCP unit lattice, remain unclear. Herein, we focused on monovalent cations, including NH4+ and Na+, which are commonly used as agents to adjust the pH and ionic strength. This study aims to demonstrate the manner in which NH4+ inhibits the intercalation of thiomalate (SH–malate), which is an antirheumatic drug precursor, into the OCP unit lattice during SH–malate-substituted OCP (OCP–SH–malate) formation. With increasing NH4+ concentration, the amount of SH–malate substituted into the OCP unit lattice decreased without a change in the crystal morphology. This characteristic is undesirable for preparing OCP combination products because NH4+, which is commonly used in the buffer solutions, will strongly inhibit the intercalation of drug molecules into OCP.