Formulation Studies on [2-amino-5-bromo-phenyl-4(3)-pyrimidinone] (ABPP), an Interferon Inducer. Anti-Cancerogenic Agent

Abstract

The apparent solubility of ABPP in aqueous solutions suitable for intravenous use was increased by cosolvent systems.

The solubility of ABPP was determined as a function of pH and concentration of NaOH, NaCl, Na₂CO₃ and co-solvents. Partition coefficient of ABPP in Octanol/water systems were also determined at various pH values. Solubility data and spectrophotemetric methods were used to determine the pKa values. The solubility of the compound increased at lower and higher pHs with increasing NaOH and Na₂CO₃ concentrations and increasing PEG 400, Propylene glycol, dimethylformamide and dimethylacetamide concentrations but decreased with the introduction of NaCl to the solution. The apparent partition coefficient of ABPP showed similar but reversed dependence to the pH of the buffer system.

From these results, suitable formulations for use as parenteral solutions are proposed. The increase in the apparent aqueous solubility of ABPP in such formulations my increase up to 800-fold, depending upon the pH and solvent concentrations. The compound was found to be stable for at least 6 months (experimental period) under normal shelf conditions when formulated for i. v. administration. When the suggested formulation injected intravenously into rabbits, at three different dose levels, the elimination half life of ABPP appeared not be dose dependent although data showed a straight line relationship between the area under the curve and dose and Cpmax ad dose.