Preparation and Characterization of Pazopanib Hydrochloride-Loaded Four-Component Self-Nanoemulsifying Drug Delivery Systems Preconcentrate for Enhanced Solubility and Dissolution

Abstract

The aim of this study was to develop a four-component self-nanoemulsifying drug delivery system (FCS) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). In the solubility test, PZH showed a highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) and was solubilized at 70 °C in the order Kollisolv PG (5.38%, w/w) > Kolliphor RH40 (0.49%) > Capmul MCM C10 (0.21%) and Capmul MCM C8 (0.19%), selected as the solubilizer, the surfactant, and the oils, respectively. In the characterization of the three-component SNEDDS (TCS) containing Kolliphor RH40/Capmul MCM C10, the particle size of dispersion was very small (95% at 120 min) at four different pHs with 1% polysorbate 80, whereas the raw PZH and Kollisolv PG solution showed a pH-dependent poor dissolution rate (about 40% at 120 min), specifically at pH 6.8 with 1% polysorbate 80. In conclusion, PZH-loaded FCS in this work demonstrated enhanced solubility and a consistent dissolution rate regardless of medium pH.

Keywords

• pazopanib hydrochloride
• pH dependence
• four-component self-nanoemulsifying drug delivery system SNEDDS
• dissolution