Hosokawa Powder Technology Foundation ANNUAL REPORT
Online ISSN : 2189-4663
ISSN-L : 2189-4663
Research Grant Report
Evaluation of Structure and Aggregation Behavior of Drug Nanoparticles by AFM and NMR
Kunikazu MORIBE
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2016 Volume 24 Pages 125-128


Aggregation behavior of a pharmaceutical drug in nanoparticles was directly evaluated using atomic force microscopy (AFM) by topographic image analysis and by force curve measurements in water. A ternary spray-dried sample (SPD) was prepared by spray drying the organic solvent containing probucol (PBC), hypromellose (HPMC), and sodium dodecyl sulfate (SDS). The amorphization of PBC in the ternary SPD was confirmed by solid-state 13C NMR measurement. A nanosuspension containing quite small particles of 25 nm was prepared after dispersion of the ternary SPD into water. Solution-state 1H NMR measurements revealed that a portion of HPMC coexisted with PBC as a mixed state in the freshly prepared nanosuspension. After storing the nanosuspension at 25°C, a gradual increase in the size of the nanoparticles was observed. AFM enabled the direct observation of the morphology and agglomeration behavior of the nanoparticles in water. AFM force–distance curves changed depending on the storage period. The stiffness increase was attributed to changes in the molecular state of PBC from the amorphous to the crystal state.

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