Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions

• DOI: 10.1021/acs.molpharmaceut.9b00158
• Publication Date: 2019-03-29T22:47:20Z
• Authors: Zhijing Zhao; Hiroaki Katai; Kenjirou Higashi; Keisuke Ueda; Kohsaku Kawakami; Kunikazu Moribe
• Keywords: Suspension

In this study, the time-dependent evolution of amorphous probucol nanoparticles was characterized by cryogenic transmission electron microscopy (cryo-TEM) and atomic force (AFM). The were formed dispersing ternary solid dispersions in water. Spray drying cogrinding used to prepare a spray-dried sample (SPD) two ground-mixture samples (GM(I) GM(II)) (PBC) form I II/hypromellose/sodium dodecyl sulfate dispersions. amorphization PBC SPDs GMs confirmed using powder X-ray diffraction (PXRD) solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Additionally, differential scanning calorimetry showed that relatively small amounts nuclei or PBC-rich domains remained both GMs. Then, physical stability drug after aqueous dispersion SPD GM suspensions during storage at 40 °C characterized. Cryogenic monitor storage. Spherical smaller than 30 nm observed all just dispersion. size particles suspension gradually increased but on order nanometers retained their spherical shape contrast, evolved through three morphologies, size, needle-like nanocrystals, micrometer-sized crystals with various shapes. suggested lower suspension. PXRD analysis freeze-dried state dispersion, while fraction exhibited crystal phase selectively crystallized its initial AFM force-distance curves also demonstrated existence molecular dependent preparation method (either completely amorphized incompletely residual drug-rich domains) determined potential mechanisms nanoparticle These findings confirm importance particle Cryo-TEM measurements provide more direct insight for designing formulations produce stable nanosuspensions efficiently improve solubility bioavailability poorly water-soluble drugs.