Simple Criterion for Stability of Aqueous Suspensions of Ultrafine Particles of a Poorly Water Soluble Drug

Abstract

In this work, a simple criterion is proposed for prediction of a long-term stability of aqueous suspensions of ultrafine particles of a poorly water soluble drug, curcumin. A new "stability parameter" (γ0ε/γε0) has been defined, which is a ratio of nondimensional mechanical (mainly ultrasonic) energy (ε/ε0) to nondimensional solid-liquid interfacial energy (γ/γ0). The stability of aqueous suspensions of curcumin particles over a period of 1 year and 9 months has been correlated with this parameter. In order to calculate this parameter, solid-liquid interfacial energies were first estimated, from nucleation rates, which in turn were calculated from size distributions of curcumin particles precipitated using water as antisolvent. The mechanical energy was then estimated from the intensity of ultrasound and mechanical agitation used during precipitation. It was found that precipitations carried out with higher values of γ0ε/γε0 (more than 100) result in aqueous suspensions with particle size less than 1 μm. It was further observed that these suspensions remain stable (i.e., no or negligible change in average particle size) for a period of 1 year and 9 months. On the other hand, the suspensions of particles precipitated at lower values of γ0ε/γε0 (less than 10) were found to be highly unstable (i.e., the average particle size changes drastically). These results suggest that γ0ε/γε0 can be used as a parameter to engineer stable aqueous suspensions of curcumin particles. Further, it was found that the use of the Mersmann equation to estimate solid-liquid interfacial surface tensions can help in making this criterion predictive.