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Flocculated Amorphous Nanoparticles for Highly Supersaturated Solutions

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Abstract

Purpose

To recover polymer-stabilized amorphous nanoparticles from aqueous dispersions efficiently by salt flocculation and to show that the particles redisperse and dissolve rapidly to produce highly supersaturated solutions.

Methods

Nanoparticle dispersions of itraconazole stabilized by nonionic polymers were formed by antisolvent precipitation and immediately flocculated with sodium sulfate, filtered and dried. The size after redispersion in water, crystallinity, and morphology were compared with those for particles produced by spray drying and rapid freezing.

Results

Particle drug loading increased to ∼90% after salt flocculation and removal of excess polymer with the filtrate. The formation of the flocs at constant particle volume fraction led to low fractal dimensions (open flocs), which facilitated redispersion in water to the original primary particle size of ∼300 nm. Amorphous particles, which were preserved throughout the flocculation–filtration–drying process, dissolved to supersaturation levels of up to 14 in pH 6.8 media. In contrast, both spray dried and rapidly frozen nanoparticle dispersions crystallized and did not produce submicron particle dispersions upon addition to water, nor high supersaturation values.

Conclusions

Salt flocculation produces large yields of high surface area amorphous nanoparticle powders that de-aggregate and dissolve rapidly upon redispersion in pH 6.8 media, for supersaturation levels up to 14.

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Acknowledgments

We gratefully acknowledge the financial support from The Dow Chemical Company (Midland, MI). This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement No. CHE-9876674 and the Welch Foundation.

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Authors and Affiliations

  1. Department of Chemical Engineering, The University of Texas at Austin, 1 University Station CO400, Austin, Texas, 78712, USA

    Michal E. Matteucci, Joseph C. Paguio, Maria A. Miller & Keith P. Johnston

  2. College of Pharmacy, University of Texas at Austin, Austin, Texas, 78712, USA

    Robert O. Williams III

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  1. Michal E. Matteucci
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  2. Joseph C. Paguio
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  3. Maria A. Miller
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  4. Robert O. Williams III
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  5. Keith P. Johnston
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Correspondence to Keith P. Johnston.

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Matteucci, M.E., Paguio, J.C., Miller, M.A. et al. Flocculated Amorphous Nanoparticles for Highly Supersaturated Solutions. Pharm Res 25, 2477–2487 (2008). https://doi.org/10.1007/s11095-008-9659-3

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  • DOI: https://doi.org/10.1007/s11095-008-9659-3

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