Synergistic effect of Soluplus and hyaluronic acid on the supersaturation maintenance of lovastatin: The facilitated in vitro-in vivo performance and improved physical stability.

The objective of present study was to explore whether polysaccharide could be employed as potential crystal growth inhibitor and provides synergistic effect on the supersaturation maintaining of lovastatin (LOV) in combination of nucleation inhibitor. Soluplus (SOL) and hyaluronic acid (HA) were selected as the most effective nucleation and crystal growth inhibitor respectively. The interaction between SOL and HA was elucidated via characterizing the particle size, zeta potential, surface hydrophobicity, solvent relaxation time (T) and FT-IR. The supersaturated drug solution was spray dried into amorphous solid dispersion, then, the in vitro release, moisture uptake and physical stability were investigated. The synergistic effect between SOL and HA was dependent on drug concentration, drug/carrier and SOL/HA weight ratio, which facilitated both in vitro and in vivo performance. It was disclosed that HA could insert into SOL structure providing both electrostatic and steric stabilization. In conclusion, the combination of nucleation and crystal growth inhibitors is a promising approach for supersaturated drug delivery system.