Solubility and distribution coefficient of potassium and magnesium retaining triamterene derivatives

Owing to its poor water solubility, there is currently no commercially available injectable formulation of the diuretic triamterene. In this study the correlation between the solubility S and the apparent distribution coefficient P-a of several potassium and magnesium retaining triamterene derivatives was examined, with a view to establishing a basis for optimizing their water solubility and pharmacological properties. Although S and P-a were inversely related for all derivatives, the equations of best-fit for the correlation differed between derivatives with neutral or basic side-chains and derivatives with acidic side-chains. The solubility of triamterene derivatives with neutral or basic side-chains is dependent on the hydrophilic properties of the side-chain, with introduction of heteroatoms (N, O) onto the side-chain leading to an increase in water solubility. The solubility of triamterene derivatives with acidic side-chains, in contrast, appears to be dependent on steric hindrance effects as well as on the hydrophilic properties of the substituents of the side-chain.