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An Investigation of Nifedipine Miscibility in Solid Dispersions Using Raman Spectroscopy

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Abstract

Purpose

Raman spectroscopy is potentially an extremely useful tool for the understanding of drug-polymer interactions in solid dispersions. This is examined and demonstrated for the case of solid dispersions of nifedipine in a polymeric substrate.

Methods

Solid dispersions consisting of nifedipine and polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer (Soluplus®) were prepared by freeze drying, melting and solvent evaporation at drug loadings of 10, 30, 50, 70 and 90% w/w. Drug-polymer interactions in the amorphous solid dispersion were estimated by Raman spectroscopy. The correlation between the solid state stability of the drug in a solid dispersion and the extent of drug-polymer interaction was monitored by X-ray diffractometry.

Results

The miscibility limit of nifedipine-Soluplus® was found to be 30% w/w drug loading for all preparation methods. The drug was found to interact with Soluplus®, through a hydrophilic interaction identified by infrared spectroscopy and a hydrophobic interaction which could be quantified by Raman spectroscopy. The average extent of the drug-polymer interaction in the studied amorphous samples at equivalent drug loading was similar, regardless of the preparation method. Inhomogeneities in samples prepared by melting contributed to a wider variation in drug-polymer interaction and poorer solid state stability, in terms of its crystallization tendency.

Conclusions

Raman spectroscopy was shown to be a useful technique in classifying miscibility levels based on the hydrophobic interaction between the drug and the polymer. Different drug loadings showed varying degrees of drug-polymer interaction, and hence variable solid state stability of the solid dispersion.

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Abbreviations

am-NIF:

Amorphous nifedipine

DSC:

Differential scanning calorimetry

FD:

Freeze drying

HPLC:

High performance liquid chromatography

IR:

Infrared spectroscopy

MAS:

Magic angle spinning

ME:

Melting

Min:

Minute

SE:

Solvent evaporation

ss-NMR:

Solid state-nuclear magnetic resonance

Tg :

Glass transition temperature

XPS:

X-ray photoelectron spectroscopy

XRD:

X-ray powder diffraction; X-ray powder diffractometry

α-NIF:

Nifedipine crystalline α-form

β-NIF:

Nifedipine crystalline β-form

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ACKNOWLEDGEMENTS AND DISCLOSURES

This research has been supported by the Ratchadaphiseksomphot Endowment Fund 2013 of Chulalongkorn University (CU-56-649-HR). The authors also wish to thank Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University and Chulalongkorn University Centenary Academic Development Project for providing research facilities. Thanks also to Dr John Kendrick for editing and comments on the manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Patumwan, Bangkok, 10330, Thailand

    Sujinda Keratichewanun, Narueporn Sutanthavibul & Jittima Chatchawalsaisin

  2. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan

    Yasuo Yoshihashi & Katsuhide Terada

  3. Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Patumwan, Bangkok, 10330, Thailand

    Narueporn Sutanthavibul & Jittima Chatchawalsaisin

Authors
  1. Sujinda Keratichewanun
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  2. Yasuo Yoshihashi
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  3. Narueporn Sutanthavibul
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Correspondence to Jittima Chatchawalsaisin.

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Keratichewanun, S., Yoshihashi, Y., Sutanthavibul, N. et al. An Investigation of Nifedipine Miscibility in Solid Dispersions Using Raman Spectroscopy. Pharm Res 32, 2458–2473 (2015). https://doi.org/10.1007/s11095-015-1638-x

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  • DOI: https://doi.org/10.1007/s11095-015-1638-x

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