Molecular-level characterization of probucol nanocrystal in water by in situ solid-state NMR spectroscopy

• Published in: International journal of pharmaceutics Vol. 423; no. 2; pp. 571 - 576
• Main Authors: Zhang, Junying, Higashi, Kenjirou, Limwikrant, Waree, Moribe, Kunikazu, Yamamoto, Keiji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.02.2012
• Subjects: additives; Carbon Isotopes; Chemistry, Pharmaceutical; Co-grinding; Colloids; Cryo-SEM; Cryoelectron Microscopy; Crystallization; Crystallography, X-Ray; electron microscopy; Freeze Drying; In situ solid-state NMR; Light; light scattering; Magnetic Resonance Spectroscopy; Microscopy, Electron, Scanning; Nanocrystal; nanocrystals; Nanoparticles; Nanotechnology; nuclear magnetic resonance spectroscopy; Particle Size; Povidone - chemistry; Powder Diffraction; probucol; Probucol - chemistry; PXRD; Scattering, Radiation; Sodium Dodecyl Sulfate - chemistry; surface interactions; Surface-Active Agents - chemistry; Technology, Pharmaceutical - methods; Water - chemistry; X-ray diffraction; Cryo-SEM; In situ solid-state NMR; Co-grinding; Nanocrystal; PXRD
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.11.028

The molecular state of colloidal probucol nanoparticles with additives was evaluated by 13C in situ solid-state NMR spectroscopy. The nanoparticles were obtained by dispersing a ternary co-ground mixture of probucol/polyvinylpyrrolidon (PVP)/sodium dodecyl sulfate (SDS) in water. Their mean particle size was found to be approximately 150nm by dynamic light scattering and cryogenic-scanning electron microscopy measurements. The results of the 13C in situ solid-state NMR spectroscopy showed that probucol existed in the crystalline state (form I) in water. 13C liquid-state NMR results indicated that PVP and SDS interacted with probucol in water. Their broad signals suggested that the surface interaction of the probucol nanocrystal with PVP and SDS stabilized the suspension. In addition, a freeze-dried sample of the suspension was studied by 13C solid-state NMR and powder X-ray diffraction experiments, which confirmed the presence of the probucol nanocrystals. The combination of the in situ solid-state, solid-state, and liquid-state NMR measurement results provided molecular-level insights about the role of intermolecular interactions in the design of nanoformulations.