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Elucidation of Compression-Induced Surface Crystallization in Amorphous Tablets Using Sum Frequency Generation (SFG) Microscopy

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Abstract

Purpose

To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods.

Method

Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy.

Results

Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage.

Conclusions

SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.

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Abbreviations

ATR-FTIR:

Attenuated total reflectance Fourier transform infrared

DSC:

Differential scanning calorimetry

HPMCAS:

Hydroxypropyl methylcellulose acetate succinate

HyD:

Hybrid detector

IR:

Infrared

MCC:

Microcrystalline cellulose

NMR:

Nuclear magnetic resonance

OPO:

Optical parametric oscillator

PEG:

Polyethylene glycol

PMT:

Photomultiplier tube

SEM:

Scanning electron microscopy

SFG:

Sum frequency generation

SHG:

Second harmonic generation

XRPD:

X-ray powder diffractometry

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was partially supported by the Pharmacy Grant 2013 (University of Helsinki). Elman Poole Travelling Fellowship and the University of Otago Doctoral Scholarship are gratefully acknowledged for providing Pei Ting Mah with financial support. Timo Laaksonen acknowledges funding from the Academy of Finland grant no. 258114.

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Author notes

    Authors and Affiliations

    1. School of Pharmacy, University of Otago, Dunedin, New Zealand

      Pei T. Mah

    2. Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

      Pei T. Mah, Dunja Novakovic, Jukka Saarinen, Stijn Van Landeghem, Leena Peltonen & Clare J. Strachan

    3. Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

      Timo Laaksonen

    4. Department of Chemistry and Bioengineering, Faculty of Natural Sciences, Tampere University of Technology, Tampere, Finland

      Timo Laaksonen

    5. Biomedicum Imaging Unit, Department of Anatomy, Medicum, Faculty of Medicine, FIN-00014 University of Helsinki, Haartmaninkatu 8, P.O. Box 63, Helsinki, Finland

      Antti Isomäki

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    1. Pei T. Mah
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    Correspondence to Antti Isomäki.

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    Dunja Novakovic and Jukka Saarinen contributed equally to this work.

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    Mah, P.T., Novakovic, D., Saarinen, J. et al. Elucidation of Compression-Induced Surface Crystallization in Amorphous Tablets Using Sum Frequency Generation (SFG) Microscopy. Pharm Res 34, 957–970 (2017). https://doi.org/10.1007/s11095-016-2046-6

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