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Temperature-Induced Surface Effects on Drug Nanosuspensions

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ABSTRACT

Purpose

The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even though such interface effects can be of pharmaceutical relevance. Such potential effects in drug nanosuspensions were to be studied for temperatures of 25 and 37°C by using complementary surface analytical methods.

Methods

Atomic force microscopy, inverse gas chromatography and UV surface dissolution imaging were used together for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively.

Results

It was demonstrated that in case of bezafibrate nanosuspension, a surface modification occurred at 37°C compared to 25°C, which notably affected dissolution rate. By contrast, no similar effect was observed in case of fenofibrate nanoparticles.

Conclusions

The combined usage of analytical surface methods provides the basis for a better understanding of phenomena that take place on drug surfaces. Such understanding is of importance for pharmaceutical development to achieve desirable quality attributes of nanosuspensions.

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Abbreviations

AFM:

Atomic force microscopy

BF:

Bezafibrate

BFns:

Bezafibrate nanosuspension

DLS:

Dynamic light scattering

DSC:

Differential scanning calorimetry

DWS:

Diffusing wave spectroscopy

FF:

Fenofibrate

FFns:

Fenofibrate nanosuspension

HPC:

Hydroxypropyl cellulose

iGC:

Inverse gas chromatography

ORD:

Optical rotatory dispersion

PXRD:

Powder X-ray diffraction

SDS:

Sodium dodecyl sulfate

SEM:

Scanning electron microscopy

WAXS:

Wide angle X-ray scattering

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ACKNOWLEDGMENTS AND DISCLOSURES

Prof. Raffaele Mezzenga is acknowledged for his support to conduct the ORD and WAXS experiments at the ETH in Zurich Switzerland. Author contributions: The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

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Authors and Affiliations

  1. Institute of Pharma Technology, University of Applied Sciences Northwest, Switzerland, Gründenstrasse 40, Basel, Switzerland

    Simone Aleandri, Andres Niederquell & Martin Kuentz

  2. Swiss Nanoscience Institute, Nano Imaging Lab, University of Basel, Klingelbergstrasse 82, Basel, Switzerland

    Monica Schönenberger

Authors
  1. Simone Aleandri
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  2. Monica Schönenberger
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  3. Andres Niederquell
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  4. Martin Kuentz
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Corresponding author

Correspondence to Martin Kuentz.

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Aleandri, S., Schönenberger, M., Niederquell, A. et al. Temperature-Induced Surface Effects on Drug Nanosuspensions. Pharm Res 35, 69 (2018). https://doi.org/10.1007/s11095-017-2300-6

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  • DOI: https://doi.org/10.1007/s11095-017-2300-6

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