Advertisement

Pharmaceutical Research

, Volume 34, Issue 5, pp 957–970 | Cite as

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

  • Pei T. Mah
  • Dunja Novakovic
  • Jukka Saarinen
  • Stijn Van Landeghem
  • Leena Peltonen
  • Timo Laaksonen
  • Antti IsomäkiEmail author
  • Clare J. Strachan
Research Paper

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.

KEY WORDS

amorphous attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy compression crystallization griseofulvin scanning electron microscopy (SEM) sum frequency generation (SFG) microscopy 

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

Notes

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.

Supplementary material

11095_2016_2046_MOESM1_ESM.docx (653 kb)
ESM 1 (DOCX 653 kb)

REFERENCES

  1. 1.
    Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44(1):235–49.CrossRefGoogle Scholar
  2. 2.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Deliv Rev. 2012;64, Supplement:4–17.Google Scholar
  3. 3.
    Elder DP, Holm R, Diego HL. Use of pharmaceutical salts and cocrystals to address the issue of poor solubility. Int J Pharm. 2013;453(1):88–100.CrossRefGoogle Scholar
  4. 4.
    Kurkov SV, Loftsson T. Cyclodextrins. Int J Pharm. 2013;453(1):167–80.CrossRefGoogle Scholar
  5. 5.
    Lu Y, Park K. Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int J Pharm. 2013;453(1):198–214.CrossRefGoogle Scholar
  6. 6.
    Möschwitzer JP. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm. 2013;453(1):142–56.CrossRefGoogle Scholar
  7. 7.
    Mu H, Holm R, Müllertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013;453(1):215–24.CrossRefGoogle Scholar
  8. 8.
    Kawakami K. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases. J Pharm Sci. 2009;98(9):2875–85.CrossRefGoogle Scholar
  9. 9.
    Babu NJ, Nangia A. Solubility advantage of amorphous drugs and pharmaceutical cocrystals. Cryst Growth Des. 2011;11(7):2662–79.CrossRefGoogle Scholar
  10. 10.
    Laitinen R, Löbmann K, Strachan CJ, Grohganz H, Rades T. Emerging trends in the stabilization of amorphous drugs. Int J Pharm. 2013;453(1):65–79.CrossRefGoogle Scholar
  11. 11.
    Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86(1):1–12.CrossRefGoogle Scholar
  12. 12.
    Yu L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Deliv Rev. 2001;48(1):27–42.CrossRefGoogle Scholar
  13. 13.
    Ayenew Z, Paudel A, Rombaut P, Mooter G. Effect of compression on non-isothermal crystallization behaviour of amorphous indomethacin. Pharm Res. 2012;29(9):2489–98.CrossRefGoogle Scholar
  14. 14.
    Thakral NK, Mohapatra S, Stephenson GA, Suryanarayanan R. Compression-induced crystallization of amorphous indomethacin in tablets: characterization of spatial heterogeneity by two-dimensional X-ray diffractometry. Mol Pharm. 2015;12(1):253–63.CrossRefGoogle Scholar
  15. 15.
    Shah B, Kakumanu VK, Bansal AK. Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharm Sci. 2006;95(8):1641–65.CrossRefGoogle Scholar
  16. 16.
    Chieng N, Rades T, Aaltonen J. An overview of recent studies on the analysis of pharmaceutical polymorphs. J Pharm Biomed Anal. 2011;55(4):618–44.CrossRefGoogle Scholar
  17. 17.
    Widjaja E, Kanaujia P, Lau G, Ng WK, Garland M, Saal C, et al. Detection of trace crystallinity in an amorphous system using Raman microscopy and chemometric analysis. Eur J Pharm Sci. 2011;42(1–2):45–54.CrossRefGoogle Scholar
  18. 18.
    Kanaujia P, Lau G, Ng WK, Widjaja E, Schreyer M, Hanefeld A, et al. Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy. Drug Dev Ind Pharm. 2011;37(9):1026–35.CrossRefGoogle Scholar
  19. 19.
    Lee CJ, Strachan CJ, Manson PJ, Rades T. Characterization of the bulk properties of pharmaceutical solids using nonlinear optics - a review. J Pharm Pharmacol. 2007;59(2):241–50.CrossRefGoogle Scholar
  20. 20.
    Schneider L, Peukert W. Second harmonic generation spectroscopy as a method for in situ and online characterization of particle surface properties. Part Part Syst Charact. 2006;23(5):351–9.CrossRefGoogle Scholar
  21. 21.
    Strachan CJ, Windbergs M, Offerhaus HL. Pharmaceutical applications of non-linear imaging. Int J Pharm. 2011;417(1–2):163–72.CrossRefGoogle Scholar
  22. 22.
    Shen Y. Surface properties probed by second-harmonic and sum-frequency generation. Nature. 1989;337:519–25.CrossRefGoogle Scholar
  23. 23.
    Zumbusch A, Holtom GR, Xie XS. Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering. Phys Rev Lett. 1999;82(20):4142.CrossRefGoogle Scholar
  24. 24.
    Strachan CJ, Lee CJ, Rades T. Partial characterization of different mixtures of solids by measuring the optical nonlinear response. J Pharm Sci. 2004;93(3):733–42.CrossRefGoogle Scholar
  25. 25.
    Chowdhury AU, Zhang S, Simpson GJ. Powders analysis by second harmonic generation microscopy. Anal Chem. 2016;88(7):3853–63.CrossRefGoogle Scholar
  26. 26.
    Schmitt PD, Trasi NS, Taylor LS, Simpson GJ. Finding the needle in the haystack: characterization of trace crystallinity in a commercial formulation of paclitaxel protein-bound particles by Raman spectroscopy enabled by second harmonic generation microscopy. Mol Pharm. 2015;12(7):2378–83.CrossRefGoogle Scholar
  27. 27.
    Zhu Q, Harris MT, Taylor LS. Modification of crystallization behavior in drug/polyethylene glycol solid dispersions. Mol Pharm. 2012;9(3):546–53.CrossRefGoogle Scholar
  28. 28.
    Zhu Q, Toth SJ, Simpson GJ, Hsu H-Y, Taylor LS, Harris MT. Crystallization and dissolution behavior of naproxen/polyethylene glycol solid dispersions. J Phys Chem B. 2013;117(5):1494–500.CrossRefGoogle Scholar
  29. 29.
    Wanapun D, Kestur US, Kissick DJ, Simpson GJ, Taylor LS. Selective detection and quantitation of organic molecule crystallization by second harmonic generation microscopy. Anal Chem. 2010;82(13):5425–32.CrossRefGoogle Scholar
  30. 30.
    Wanapun D, Kestur US, Taylor LS, Simpson GJ. Single particle nonlinear optical imaging of trace crystallinity in an organic powder. Anal Chem. 2011;83(12):4745–51.CrossRefGoogle Scholar
  31. 31.
    Kestur US, Wanapun D, Toth SJ, Wegiel LA, Simpson GJ, Taylor LS. Nonlinear optical imaging for sensitive detection of crystals in bulk amorphous powders. J Pharm Sci. 2012;101(11):4201–13.CrossRefGoogle Scholar
  32. 32.
    Hsu H-Y, Toth SJ, Simpson GJ, Taylor LS, Harris MT. Effect of substrates on naproxen-polyvinylpyrrolidone solid dispersions formed via the drop printing technique. J Pharm Sci. 2013;102(2):638–48.CrossRefGoogle Scholar
  33. 33.
    Mahieu A, Willart J-F, Dudognon E, Eddleston MD, Jones W, Danède F, et al. On the polymorphism of griseofulvin: identification of two additional polymorphs. J Pharm Sci. 2013;102(2):462–8.CrossRefGoogle Scholar
  34. 34.
    Pan Q, Guo P, Duan J, Cheng Q, Li H. Comparative crystal structure determination of griseofulvin: powder X-ray diffraction versus single-crystal X-ray diffraction. Chin Sci Bull. 2012;57(30):3867–71.CrossRefGoogle Scholar
  35. 35.
    Zoumi A, Yeh A, Tromberg BJ. Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence. Proc Natl Acad Sci. 2002;99(17):11014–9.CrossRefGoogle Scholar
  36. 36.
    Gallais L, Douti D-B, Commandre M, Batavičiūtė G, Pupka E, Ščiuka M, et al. Wavelength dependence of femtosecond laser-induced damage threshold of optical materials. J Appl Phys. 2015;117(22):223103.CrossRefGoogle Scholar
  37. 37.
    Watanabe T, Wakiyama N, Usui F, Ikeda M, Isobe T, Senna M. Stability of amorphous indomethacin compounded with silica. Int J Pharm. 2001;226(1–2):81–91.CrossRefGoogle Scholar
  38. 38.
    Wang L, Cui FD, Sunada H. Preparation and evaluation of solid dispersions of nitrendipine prepared with fine silica particles using the melt-mixing method. Chem Pharm Bull. 2006;54(1):37–43.CrossRefGoogle Scholar
  39. 39.
    Hellrup J, Alderborn G, Mahlin D. Inhibition of recrystallization of amorphous lactose in nanocomposites formed by spray-drying. J Pharm Sci. 2015;104(11):3760–9.CrossRefGoogle Scholar
  40. 40.
    Ellison CD, Ennis BJ, Hamad ML, Lyon RC. Measuring the distribution of density and tabletting force in pharmaceutical tablets by chemical imaging. J Pharm Biomed Anal. 2008;48(1):1–7.CrossRefGoogle Scholar
  41. 41.
    De Figueiredo LP, Ferreira FF. The Rietveld method as a tool to quantify the amorphous amount of microcrystalline cellulose. J Pharm Sci. 2014;103(5):1394–9.CrossRefGoogle Scholar
  42. 42.
    Takahashi Y, Tadokoro H. Structural studies of polyethers,(−(CH2)mO-)n. X. Crystal structure of poly (ethylene oxide). Macromolecules. 1973;6(5):672–5.CrossRefGoogle Scholar
  43. 43.
    Pielichowska K, Głowinkowski S, Lekki J, Biniaś D, Pielichowski K, Jenczyk J. PEO/fatty acid blends for thermal energy storage materials. Structural/morphological features and hydrogen interactions. Eur Polym J. 2008;44(10):3344–60.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Pei T. Mah
    • 1
    • 2
  • Dunja Novakovic
    • 2
  • Jukka Saarinen
    • 2
  • Stijn Van Landeghem
    • 2
  • Leena Peltonen
    • 2
  • Timo Laaksonen
    • 3
    • 4
  • Antti Isomäki
    • 5
    Email author
  • Clare J. Strachan
    • 2
  1. 1.School of PharmacyUniversity of OtagoDunedinNew Zealand
  2. 2.Division of Pharmaceutical Chemistry and Technology, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland
  3. 3.Division of Pharmaceutical Biosciences, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland
  4. 4.Department of Chemistry and Bioengineering, Faculty of Natural SciencesTampere University of TechnologyTampereFinland
  5. 5.Biomedicum Imaging Unit, Department of Anatomy, Medicum, Faculty of MedicineFIN-00014 University of HelsinkiHelsinkiFinland

Personalised recommendations