Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms

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High production output of solid pharmaceutical formulations requires fast methods to ensure their quality. Likewise, fast analytical procedures are required in forensic sciences, for example at customs, to substantiate an initial suspicion. We here present the design and the optimization of an instrumental setup for rapid and non-invasive characterization of tablets by laser-induced fluorescence spectroscopy (with a UV-laser (λ ex = 266 nm) as excitation source) in reflection geometry. The setup was first validated with regard to repeatability, bleaching phenomena, and sensitivity. The effect on the spectra by the physical and chemical properties of the samples, e.g. their hardness, homogeneity, chemical composition, and granule grain size of the uncompressed material, using a series of tablets, manufactured in accordance with design of experiments, was investigated. Investigation of tablets with regard to homogeneity, especially, is extremely important in pharmaceutical production processes. We demonstrate that multiplicative scatter correction is an appropriate tool for data preprocessing of fluorescence spectra. Tablets with different physical and chemical characteristics can be discriminated well from their fluorescence spectra by subjecting the results to principal component analysis.

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  1. 1.

    Aaltonen J, Gordon KC, Strachan CJ, Rades T (2008) Perspectives in the use of spectroscopy to characterise pharmaceutical solids. Int J Pharm 364(2):159–169

    Article  CAS  Google Scholar 

  2. 2.

    Jivraj M, Martini LG, Thomson CM (2000) An overview of the different excipients useful for the direct compression of tablets. Pharmaceut Sci Tech Today 3(2):58–63

    Article  CAS  Google Scholar 

  3. 3.

    Boukouvala F, Niotis V, Ramachandran R, Muzzio FJ, Ierapetritou MG (2012) An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process. Comput Chem Eng 42(0):30–47

    Article  CAS  Google Scholar 

  4. 4.

    Abu Bakar NF, Mujumdar A, Urabe S, Takano K, Nishii K, Horio M (2007) Improvement of sticking tendency of granules during tabletting process by pressure swing granulation. Powder Technol 176(2–3):137–147

    Article  CAS  Google Scholar 

  5. 5.

    Zarie ES, Kaidas V, Gedamu D, Mishra YK, Adelung R, Furkert FH, Scherließ R, Steckel H, Groessner-Schreiber B (2012) Solvent free fabrication of micro and nanostructured drug coatings by thermal evaporation for controlled release and increased effects. PLoS One 7(8):e40746

    Article  CAS  Google Scholar 

  6. 6.

    Rodionova OY, Houmøller LP, Pomerantsev AL, Geladi P, Burger J, Dorofeyev VL, Arzamastsev AP (2005) NIR spectrometry for counterfeit drug detection: A feasibility study. Anal Chim Acta 549(1–2):151–158

    Article  CAS  Google Scholar 

  7. 7.

    Dégardin K, Roggo Y, Been F, Margot P (2011) Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics. Anal Chim Acta 705(1):334–341

    Article  Google Scholar 

  8. 8.

    Been F, Roggo Y, Degardin K, Esseiva P, Margot P (2011) Profiling of counterfeit medicines by vibrational spectroscopy. Forensic Sci Int 211(1–3):83–100

    Article  CAS  Google Scholar 

  9. 9.

    Holzgrabe U (2009) Problem Arzneimittelfälschungen in Afrika und Südostasien. Gefälschte Antimalariamittel und mehr. Pharm Unserer Zeit 38(6):560–562

    Article  Google Scholar 

  10. 10.

    Mizobe Y, Hinoue T, Yamamoto A, Hisaki I, Miyata M, Hasegawa Y, Tohnai N (2009) Systematic Investigation of Molecular Arrangements and Solid‐State Fluorescence Properties on Salts of Anthracene‐2, 6‐disulfonic Acid with Aliphatic Primary Amines. Chem-A Eur J 15(33):8175–8184

    Article  CAS  Google Scholar 

  11. 11.

    Wehry EL (1997) Molecular fluorescence and phosphorescence spectrometry. In: Settle F (ed) Handbook of instrumental techniques for analytical chemistry, 1st. edn. Prentice Hall, Upper Saddle River

  12. 12.

    Navalón A, Blanc R, del Olmo M, Vilchez JL (1999) Simultaneous determination of naproxen, salicylic acid and acetylsalicylic acid by spectrofluorimetry using partial least-squares (PLS) multivariate calibration. Talanta 48(2):469–475

    Article  Google Scholar 

  13. 13.

    Moreira AB, Dias ILT, Neto GO, Zagatto EAG, Kubota LT (2004) Solid-phase fluorescence spectroscopy for the determination of acetylsalicylic acid in powdered pharmaceutical samples. Anal Chim Acta 523(1):49–52

    Article  CAS  Google Scholar 

  14. 14.

    Martens H, Nielsen JP, Engelsen SB (2003) Light Scattering and Light Absorbance Separated by Extended Multiplicative Signal Correction. Application to Near-Infrared Transmission Analysis of Powder Mixtures. Anal Chem 75(3):394–404

    Article  CAS  Google Scholar 

  15. 15.

    Kessler W (2007) Multivariate Datenanalyse für die Pharma-, Bio- und Prozessanalytik. Wiley-VCH, Weinheim

  16. 16.

    Heraud P, Wood BR, Beardall J, McNaughton D (2006) Effects of pre-processing of Raman spectra on in vivo classification of nutrient status of microalgal cells. J Chemom 20(5):193–197

    Article  CAS  Google Scholar 

  17. 17.

    Roggo Y, Chalus P, Maurer L, Lema-Martinez C, Edmond A, Jent N (2007) A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. J Pharm Biomed Anal 44(3):683–700

    Article  CAS  Google Scholar 

  18. 18.

    Song L, Hennink E, Young IT, Tanke HJ (1995) Photobleaching kinetics of fluorescein in quantitative fluorescence microscopy. Biophys J 68(6):2588–2600

    Article  CAS  Google Scholar 

  19. 19.

    Oujja M, Vázquez-Calvo C, Sanz M, Buergo MÁ, Fort R, Castillejo M (2012) Laser-induced fluorescence and FT-Raman spectroscopy for characterizing patinas on stone substrates. Anal Bioanal Chem 402(4):1433–1441

    Article  CAS  Google Scholar 

  20. 20.

    Kim M, Chung H, Woo Y, Kemper M (2006) New reliable Raman collection system using the wide area illumination (WAI) scheme combined with the synchronous intensity correction standard for the analysis of pharmaceutical tablets. Anal Chim Acta 579(2):209–216

    Article  CAS  Google Scholar 

  21. 21.

    Villari A, Micali N, Fresta M, Puglisi G (1992) Simultaneous spectrophotometric determination in solid phase of aspirin and its impurity salicylic acid in pharmaceutical formulations. J Pharm Sci 81(9):895–898

    Article  CAS  Google Scholar 

  22. 22.

    Head W (1961) Investigation of the applicability of solid state fluorescence to pharmaceutical analysis. J Pharm Sci 50(12):1041–1044

    Article  CAS  Google Scholar 

  23. 23.

    Edwards L (1950) The hydrolysis of aspirin. A determination of the thermodynamic dissociation constant and a study of the reaction kinetics by ultra-violet spectrophotometry. Trans Faraday Soc 46:723–735

    Article  CAS  Google Scholar 

  24. 24.

    Milofsky R, Bauer E (1997) Capillary electrophoresis with post-column addition of terbium and sensitized lanthanide-ion luminescence detection for the determination of diflunisal and salicylic acid. J High Resolut Chromatogr 20(12):638–642

    Article  CAS  Google Scholar 

  25. 25.

    Chen RF (1967) Some characteristics of the fluorescence of quinine. Anal Biochem 19(2):374–387

    Article  CAS  Google Scholar 

  26. 26.

    Merckle P, Kovar K-A (1998) Assay of effervescent tablets by near-infrared spectroscopy in transmittance and reflectance mode: acetylsalicylic acid in mono and combination formulations. J Pharm Biomed Anal 17(3):365–374

    Article  CAS  Google Scholar 

  27. 27.

    Earnshaw CJ, Carolan VA, Richards DS, Clench MR (2010) Direct analysis of pharmaceutical tablet formulations using matrix-assisted laser desorption/ionisation mass spectrometry imaging. Rapid Commun Mass Spectrom 24(11):1665–1672

    Article  CAS  Google Scholar 

  28. 28.

    Sasic S, Kong A, Kaul G (2013) Determining API domain sizes in pharmaceutical tablets and blends upon varying milling conditions by near-infrared chemical imaging. Anal Methods 5(9):2360–2368

    Article  CAS  Google Scholar 

  29. 29.

    Cruz J, Blanco M (2011) Content uniformity studies in tablets by NIR-CI. J Pharm Biomed Anal 56(2):408–412

    Article  CAS  Google Scholar 

  30. 30.

    Nakamoto K, Urasaki T, Hondo S, Murahashi N, Yonemochi E, Terada K (2013) Evaluation of the crystalline and amorphous states of drug products by nanothermal analysis and Raman imaging. J Pharm Biomed Anal 75:105–111

    Article  CAS  Google Scholar 

  31. 31.

    Puchert T, Lochmann D, Menezes JC, Reich G (2010) Near-infrared chemical imaging (NIR-CI) for counterfeit drug identification—A four-stage concept with a novel approach of data processing (Linear Image Signature). J Pharm Biomed Anal 51(1):138–145

    Article  CAS  Google Scholar 

  32. 32.

    Vredenbregt MJ, Blok-Tip L, Hoogerbrugge R, Barends DM, Dd K (2006) Screening suspected counterfeit Viagra® and imitations of Viagra® with near-infrared spectroscopy. J Pharm Biomed Anal 40(4):840–849

    Article  CAS  Google Scholar 

  33. 33.

    Lai C-K, Holt D, Leung JC, Cooney CL, Raju GK, Hansen P (2001) Real time and noninvasive monitoring of dry powder blend homogeneity. AlChE J 47(11):2618–2622

    Article  CAS  Google Scholar 

  34. 34.

    Morisseau K, Rhodes C (1997) Near-Infrared Spectroscopy as a Nondestructive Alternative to Conventional Tablet Hardness Testing. Pharm Res 14(1):108–111

    Article  CAS  Google Scholar 

  35. 35.

    Blanco M, Alcalá M, González JM, Torras E (2006) A process analytical technology approach based on near infrared spectroscopy: Tablet hardness, content uniformity, and dissolution test measurements of intact tablets. J Pharm Sci 95(10):2137–2144

    Article  CAS  Google Scholar 

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We thank Jennifer Oppenberg (University of Münster, Germany) for her introduction to the fabrication of tablets. The help of Dr Jan Pöggeler (Forschungszentrum Jülich, Germany) is gratefully acknowledged. This project was partially funded by the Federal Ministry of Education and Research (BMBF), FZK: 13 N12012. This work was partially funded by the Excellence Initiative, a jointly funded program of the German federal and state governments, organized by the German Research Foundation (DFG).

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Correspondence to Carolin Huhn.

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Woltmann, E., Meyer, H., Weigel, D. et al. Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms. Anal Bioanal Chem 406, 6347–6362 (2014).

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  • Tablet analysis
  • Solid-state fluorescence spectroscopy
  • Grain size
  • Photobleaching
  • Scattering effects
  • Homogeneity