Multi-faceted Characterization of Wet-milled Griseofulvin Nanosuspensions for Elucidation of Aggregation State and Stabilization Mechanisms

Document Type

Article

Publication Date

5-1-2018

Abstract

Characterization of wet-milled drug suspensions containing neutral polymer–anionic surfactant as stabilizers poses unique challenges in terms of assessing the aggregation state and examining the stabilization mechanisms. Using a multi-faceted characterization method, this study aims to assess the aggregation state of wet-milled griseofulvin (GF) nanosuspensions and elucidate the stabilization mechanisms and impact of stabilizers. Two grades, SSL and L, of hydroxypropyl cellulose (HPC) with molecular weights of 40 and 140 kg/mol, respectively, were used as a neutral stabilizer at concentrations varying from 0 to 7.5% (w/w) without and with 0.05% (w/w) sodium dodecyl sulfate (SDS). The aggregation state was examined via laser diffraction, scanning electron microscope (SEM) imaging, and rheometry. Zeta potential, stabilizer adsorption, surface tension, and drug wettability were used to elucidate the stabilization mechanisms. The results suggest that deviation from a uni-modal PSD and pronounced pseudoplasticity with power–law index lower than one signify severe aggregation. Polymer or surfactant alone was not able to prevent GF nanoparticle aggregation, whereas HPC–SDS combination led to synergistic stabilization. The effect of polymer concentration was explained mainly by the stabilizer adsorption and partly by surface tension. The synergistic stabilization afforded by HPC–SDS, traditionally explained by electrosteric mechanism, was attributed to steric stabilization provided by HPC and enhanced GF wettability/reduced surface tension provided by SDS. Zeta potential results could not explain the mitigation of aggregation by HPC–SDS. Overall, this study has demonstrated that the elucidation of the complex effects of HPC–SDS on GF nanosuspension stability entails a multi-faceted and comprehensive characterization approach.

Identifier

85044574409 (Scopus)

Publication Title

AAPS Pharmscitech

External Full Text Location

https://doi.org/10.1208/s12249-018-0993-4

e-ISSN

15309932

PubMed ID

29603084

First Page

1789

Last Page

1801

Issue

4

Volume

19

Grant

EEC-0540855

Fund Ref

National Science Foundation

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