Preparation of a ternary amorphous solid dispersion using hot-melt extrusion for obtaining a stable colloidal dispersion of amorphous probucol nanoparticles
In our previous reports, ternary amorphous solid dispersions (ASDs) of probucol (PBC)/polymer/surfactant were prepared by spray-drying and cryo-grinding, and colloidal dispersions of amorphous PBC nanoparticles were obtained by dispersing the ternary ASD into water. In this study, hot-melt extrusion, which is a practical method for preparing ASD formulations, to obtain ternary ASDs and colloidal dispersions of amorphous PBC nanoparticles. Polyvinylpyrrolidone (PVP) K12, with a relatively low Tg, below 100°C, was used as a polymer, while poloxamer P407 (P407), which remains chemically stable during the hot-melt extrusion process, was utilized as a surfactant. Ternary ASDs were successfully produced with high-weight ratios of PVP and P407. A hydrogen bond between the PBC hydroxyl proton and PVP carbonyl oxygen in the ternary ASD was detected using solid-state NMR spectroscopy, which suggested that amorphous PBC was mainly stabilized by PVP.
Stable colloidal dispersions of amorphous PBC nanoparticles were obtained from the PBC/PVP/P407 ASD, at a weight ratio of 1:4:2. The mean particle size was below 200 nm and the amorphous state of PBC remained stable upon storage at 25°C for 14 d. Solution-state 1H NMR and zeta-potential measurements suggested that P407 mainly stabilized the colloidal dispersion of amorphous PBC nanoparticles, by steric hindrance at the solid/liquid interface. The findings of this study demonstrate that, similar to spray-drying, hot-melt extrusion can form practical ternary ASDs that provide colloidal dispersion of amorphous drug nanoparticles. Thus, this study advocates for the use of hot-melt extrusion in the design of an amorphous formulation for a variety of poorly water-soluble drugs.
Read more
Materials
PBC form I (Mw: 516,84) was purchased from Tokyo Chemical Industry Co. Ltd. (Tokyo, Japan). PVP K12 (Mw: 2,500) and P407 (Mw: 9,840–14,600) were provided by BASF Japan Ltd. (Tokyo, Japan). Hydroxypropyl cellulose (HPC)-SSL was purchased from Nippon Soda Co. Ltd. SDS (Mw: 288,38) was purchased from Wako Pure Chemical Industries Ltd (Osaka, Japan).
Naho Hanada, Kenjirou Higashi, Zhijing Zhao, Keisuke Ueda, Kunikazu Moribe, Preparation of a ternary amorphous solid dispersion using hot-melt extrusion for obtaining a stable colloidal dispersion of amorphous probucol nanoparticles, International Journal of Pharmaceutics, 2023, 122959, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.122959.
Read more on Disintegrants – Pharmaceutical Excipients here:
