Hard to Wet Surfaces (Eli Lilly-Hard to Wet Surfaces)
The Hard to Wet Surfaces (Eli Lilly-Hard to Wet Surfaces) investigation is simple, safe, and similar to the standard dissolution experiments run at Eli Lilly. Observing the performance of mini-tablet wetting and dissolution in a controlled situation in a vial helps to establish increased understanding of how a tablet/formulation performs in-vivo.
On earth, the density differences between a hard-to-wet solid/tablet and the solution can result in the solid/tablet floating on top of the solution, thereby exacerbating the dissolution problem. In microgravity, the solid/liquid density differences are negligible, and other factors controlling dissolution rate such as wettability dominate.
Key questions include how the mini-tablet behaves differently in microgravity (float vs. sink, wet out faster or slower, etc.), and will simple mixing have less impact in microgravity (will the tablet/capsule move less?). The mini tablets may also provide some insight into how they dissolve in situ, but are really being used because of the well understood surface and size in the dissolution experiments.
Mini tablets are pre-formed by pressing standard extended-release excipient (hypromellose acetate succinate, HPMCAS) into a standard size tablet. Tablets with two different densities are prepared: one with a density > 1 mg/mL and one with a density < 1mg/mL. A series of 12 vials are preloaded with a magnetic stir bar and single tablet: 6 vials with the less dense tablets, and 6 vials with the more dense tablets. Phosphate buffer is added to each vial via syringe, and the rate of dissolution visually recorded by camera. Intermittent mixing of the vials (once every 30 minutes) by moving the internal mixing magnet up and down within the vial prevents a formation of a concentration gradient, which may complicate results. The rate of dissolution is compared to the ground control samples. Additional analysis of the photographic results is also carried out to analyze the effect of microgravity on dissolution behavior.