Morphology and Surface States of Colloidal Probucol Nanoparticles Evaluated by Atomic Force Microscopy

Abstract

Morphology and surface states of colloidal probucol nanoparticles after dispersion of probucol/polyvinylpyrrolidone (PVP)/sodium dodecyl sulphate (SDS) ternary ground mixture into water were investigated by atomic force microscopy (AFM). The observed particles had core-shell structure, i.e. drug nanocrystals were covered with PVP and SDS complex. The AFM phase image and the force curve analyses indicated that probucol nanoparticles with PVP K17 showed layer structure, compared to those with PVPK12. The structural difference was explainable in terms of the molecular states of PVP-SDS complex on the particle surface. These findings support not only the mechanism of drug nanoparticle formation but also the in vivo absorption results with the almost same particle size of ca. 40 nm.Key words atomic force microscopy; colloidal nanoparticle; surface state; grinding; probucol Co-grinding, where a drug is ground together with excipients, is a promising method for an effective reduction of particle size. A certain number of studies revealed that the coground mixture enhanced dissolution, resulting in the improvement of oral absorption and bioavailability.1-3) Wet cogrinding method has been known as an effective method to produce stable nanosuspensions.4-7) Liversidge and Cundy proposed a preparation method for crystalline nanoparticle by wet co-grinding of danazol with polyvinylpyrrolidone (PVP).4) Oral absorption of poorly water-soluble drugs in nanocrystal form was remarkably improved. 4,5) Shi et al. reported the image of drug nanocrystals in the formulation by atomic force microscopy and complementary techniques. 8)They showed the morphology of nanocrystals, though the surface states of the nanocrystals were not well characterized.Compared with the wet co-grinding method, the dry cogrinding process has some advantages for solid pharmaceutical applications due to its simple preparation with free solvents. Our previous studies demonstrated that drug nanoparticle was successfully produced by the dry co-grinding of a poorly water-soluble drug with PVP and sodium dodecyl sulfate (SDS).9-11) When probucol, which is mainly used as a cholesterol-lowering agent, was used as a model drug, solidstate 13 C-NMR studies revealed that the nanoparticle formation and stabilization were attributable to grinding-induced solid-state interactions among components of the drug/ PVP/SDS ternary system.12) The agglomeration of colloidal nanoparticles after dispersing the ground mixture (GM) into water was effectively inhibited in the presence of PVP and SDS. The results of particle size and zeta-potential measurements suggested that the adsorption of both PVP and SDS as the complex on the surface of crystalline particles stabilized the drug nanoparticles.13) Because surface states of the probucol nanoparticles certainly affected the dissolution and the subsequent absorption, the direct observation of the nanoparticles in aqueous environment was an urgent requisite. We have observed the morphology of probucol nanoparticles in water by environm...

Performance Parameters and Characterizations of Nanocrystals: A Brief Review

“…The structural difference was accountable in terms of the molecular states of PVP-SDS complex on the particle surface. These findings support not only the mechanism of drug nanoparticle formation but also the in vivo absorption results with the almost same particle size of 40 nm [ 36 ].…”

Diverse deformation properties of polymeric nanocapsules and lipid-core nanocapsules

“…The two-slope behavior possibly represents a signature of core-shell structures. 42 For the NC particles the first slope value was 0.43 and the second slope value was 0.67 while for the LNC particles these values were 0.65 and 0.81, respectively. It can be noted that the difference between the slopes was close to 40% for NCs and 20% for LNCs in comparison with the substrate.…”

Design of Dry Nanosuspension with Highly Spontaneous Dispersible Characteristics to Develop Solubilized Formulation for Poorly Water-Soluble Drugs

“…It was found that the high redispersiblility of Sus-SD products was reproducible among batches even if the conditions of spray-drying process were changed. It was also reported that the ternary ground mixture of drug/PVP/SLS could produce the colloidal drug nanoparticles when dispersing in water (34,35). From the human health point of view, it would be greatly advantageous that the nano-dispersion was achieved with much higher drug content (drug:PVP:SLS=40:5:1) in this study compared to the previous one (drug:PVP:SLS=1:3:1).…”