On the usefulness of sink index in characterizing the degree of nonsinkness in dissolution studies

Abstract

To accurately quantify the nonsinkness in dissolution testing of supersaturating formulations, our group previously introduced a dimensionless Sink Index (SI): SI = Cs/(Dose/V), where Cs is the solubility of crystalline drug, V the volume of dissolution medium, and Dose the total amount of drug in the test sample. The objective of this study is to test whether one can consistently generate similar (or superimposable) kinetic solubility profiles (KSP) from a given amorphous solid dispersion (ASD) with different volume, type of dissolution medium, and/or total dose as long as the SI value is kept constant. Dissolution results based on ASDs of model drugs fenofibrate, indomethacin, and posaconazole in polyvinylpyrrolidone and poly(2-hydroxyethyl methacrylate) show that similar (or superimposable) kinetic solubility profiles (relative difference f1 < 15) for ASDs can be achieved when conducting dissolution studies in the same dissolution medium (i.e., same composition and pH), irrespective of variations in medium volume, scale of USP dissolution apparatus, or total dose, as long as the SI value is kept constant. However, maintaining a constant SI did not generate similar kinetic solubility profiles when two different buffer media were compared (f1 ≫ 15) due to changes in API solubility and the final concentration in different media.