Pharmaceutical Research

, Volume 31, Issue 8, pp 2140–2151 | Cite as

Evaluation of Coating Properties of Enteric-Coated Tablets Using Terahertz Pulsed Imaging

Research Paper

ABSTRACT

Purpose

Enteric coatings are used to reduce gastrointestinal side effects and control the release properties of oral medications. Although widely used, the effect of formulation and process conditions on physicochemical and functional properties of enteric coatings remains unclear.

Methods

Terahertz pulsed imaging (TPI) was employed to evaluate the coat properties of enteric coated tablets (ECTs) with various acid resistance. Other analytic methods, such as loss on drying, scanning electron microscopy and X-ray computed tomography were then used to validate the relationships established among 4 TPI-derived parameters and the physicochemical properties of enteric coatings.

Results

Weight gain measurement did not provide any information to assess acid resistance of enteric coating, whereas four TPI-derived parameters non-destructively reflected the coating properties such as thickness, coat uniformity, density, and water distribution, allowing the identification of the causes of poor acid resistance in certain ECT batches using a single measurement. These parameters also revealed the effect of coating conditions; in particular, coating under dry conditions led to less dense and nonuniform coatings with poor acid resistance.

Conclusion

We demonstrated the utility of TPI to identify structural defects within ECTs with poor acid resistance. TPI-derived parameters can aid in formulation development and quality control of ECTs.

KEY WORDS

acid uptake coating uniformity enteric coated tablets terahertz pulsed imaging X-ray CT scan 

ABBREVIATIONS

ANOVA

Analysis of variance

API

Active pharmaceutical ingredient

ECT

Enteric coated tablet

LOD

Loss on drying

MFT

Minimum film forming temperature

NIR

Near infrared spectroscopy

SEM

Scanning electron microscopy

TEFPS

Terahertz electric field peak strength

TPI

Terahertz pulsed imaging

XRCT

X-ray computed tomography

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to acknowledge the help of Muneo Nonomura and Ayako Baba in Takeda, Tsuyoshi Miura from Bruker Optics, Jesse Alton and Philip F Taday from Teraview for their valuable suggestions and assistance with this study, which has been a great aid toward the publication of this paper.

REFERENCES

  1. 1.
    Felton LA, Porter SC. An update on pharmaceutical film coating for drug delivery. Expert Opin Drug Deliv. 2013;10:421–35.PubMedCrossRefGoogle Scholar
  2. 2.
    Missaghi S, Young C, Fegely K, Rajabi-Siahboomi AR. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies. Drug Dev Ind Pharm. 2010;36(2):180–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Fock K, Ang T, Bee L, Lee E. Proton pump inhibitors. Clin Pharmacokinet. 2008;47(1):1–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Maghsoodi M. Physicomechanical properties of naproxen-loaded microparticles prepared from Eudragit l100. AAPS PharmSciTech. 2009;10(1):120–8.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Emerson CR, Marzella N. Dexlansoprazole: a proton pump inhibitor with a dual delayed-release system. Clin Ther. 2010;32(9):1578–96.PubMedCrossRefGoogle Scholar
  6. 6.
    Felton LA, Porter SC. Guest editor’s comments. Drug Dev Ind Pharm. 2010;36(2):127.PubMedCrossRefGoogle Scholar
  7. 7.
    Suzzi D, Radl S, Khinast JG. Local analysis of the tablet coating process: impact of operation conditions on film quality. Chem Eng Sci. 2010;65(21):5699–715.CrossRefGoogle Scholar
  8. 8.
    Ho L, Müller R, Römer M, Gordon KC, Heinämäki J, Kleinebudde P, et al. Analysis of sustained-release tablet film coats using terahertz pulsed imaging. J Control Release. 2007;119(3):253–61.PubMedCrossRefGoogle Scholar
  9. 9.
    Ho L, Müller R, Gordon KC, Kleinebudde P, Pepper M, Rades T, et al. Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance. J Control Release. 2008;127(1):79–87.PubMedCrossRefGoogle Scholar
  10. 10.
    Thoma K, Bechtold K. Influence of aqueous coatings on the stability of enteric coated pellets and tablets. Eur J Pharm Biopharm. 1999;47(1):39–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Perfetti G, Van de Casteele E, Rieger B, Wildeboer WJ, Meesters GMH. X-ray micro tomography and image analysis as complementary methods for morphological characterization and coating thickness measurement of coated particles. Adv Powder Technol. 2010;21(6):663–75.CrossRefGoogle Scholar
  12. 12.
    Perfetti G, Alphazan T, van Hee P, Wildeboer WJ, Meesters GMH. Relation between surface roughness of free films and process parameters in spray coating. Eur J Pharm Sci. 2011;42(3):262–72.PubMedCrossRefGoogle Scholar
  13. 13.
    Madamba MC, Mullett W, Debnath S, Kwong E. Characterization of tablet film coatings using a laser-induced breakdown spectroscopic technique. AAPS PharmSciTech. 2007;8(4):184–90.PubMedCentralCrossRefGoogle Scholar
  14. 14.
    Kirsch J, Drennen J. Near-infrared spectroscopic monitoring of the film coating process. Pharm Res. 1996;13(2):234–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Hagrasy A, Chang S-Y, Desai D, Kiang S. Raman spectroscopy for the determination of coating uniformity of tablets: assessment of product quality and coating pan mixing efficiency during scale-up. J Pharm Innov. 2006;1(1):37–42.CrossRefGoogle Scholar
  16. 16.
    Seitavuopio P, Rantanen J, Yliruusi J. Tablet surface characterisation by various imaging techniques. Int J Pharm. 2003;254(2):281–6.PubMedCrossRefGoogle Scholar
  17. 17.
    May RK, Evans MJ, Zhong S, Warr I, Gladden LF, Shen Y, et al. Terahertz in-line sensor for direct coating thickness measurement of individual tablets during film coating in real-time. J Pharm Sci. 2011;100(4):1535–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Momose W, Yoshino H, Katakawa Y, Yamashita K, Imai K, Sako K, et al. Applying terahertz technology for nondestructive detection of crack initiation in a film-coated layer on a swelling tablet. Results Pharma Sci. 2012;2:29–37.CrossRefGoogle Scholar
  19. 19.
    Shen Y-C. Terahertz pulsed spectroscopy and imaging for pharmaceutical applications: a review. Int J Pharm. 2011;417(1–2):48–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Zeitler JA, Taday PF, Newnham DA, Pepper M, Gordon KC, Rades T. Terahertz pulsed spectroscopy and imaging in the pharmaceutical setting—a review. J Pharm Pharmacol. 2007;59(2):209–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Zeitler JA, Gladden LF. In-vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms. Eur J Pharm Biopharm. 2009;71(1):2–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Spencer JA, Gao Z, Moore T, Buhse LF, Taday PF, Newnham DA, et al. Delayed release tablet dissolution related to coating thickness by terahertz pulsed image mapping. J Pharm Sci. 2008;97(4):1543–50.PubMedCrossRefGoogle Scholar
  23. 23.
    May RK, Su K, Han L, Zhong S, Elliott JA, Gladden LF, et al. Hardness and density distributions of pharmaceutical tablets measured by terahertz pulsed imaging. J Pharm Sci. 2013;102(7):2179–86.PubMedCrossRefGoogle Scholar
  24. 24.
    Niwa M, Hiraishi Y. Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging. Int J Pharm. 2014;461(1–2):342–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Niwa M, Hiraishi Y, Iwasaki N, Terada K. Quantitative analysis of the layer separation risk in bilayer tablets using terahertz pulsed imaging. Int J Pharm. 2013;452(1–2):249–56.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang J, Hemenway J, Chen W, Desai D, Early W, Paruchuri S, et al. An evaluation of process parameters to improve coating efficiency of an active tablet film-coating process. Int J Pharm. 2012;427(2):163–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Shen YC, Taday PF. Development and application of terahertz pulsed imaging for nondestructive inspection of pharmaceutical tablet. IEEE J Sel Top Quantum Electron. 2008;14:407–15.CrossRefGoogle Scholar
  28. 28.
    Brock D, Zeitler JA, Funke A, Knop K, Kleinebudde P. Critical factors in the measurement of tablet film coatings using terahertz pulsed imaging. J Pharm Sci. 2013;102(6):1813–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Liu F, Merchant HA, Kulkarni RP, Alkademi M, Basit AW. Evolution of a physiological pH6.8 bicarbonate buffer system: application to the dissolution testing of enteric coated products. Eur J Pharm Biopharm. 2011;78(1):151–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Jördens C, Wietzke S, Scheller M, Koch M. Investigation of the water absorption in polyamide and wood plastic composite by terahertz time-domain spectroscopy. Polym Test. 2010;29(2):209–15.CrossRefGoogle Scholar
  31. 31.
    Ludwig I, Schabel W, Ferlin P, Castaing JC, Kind M. Drying, film formation and open time of aqueous polymer dispersions. Eur Phys J Spec Top. 2009;166(1):39–43.CrossRefGoogle Scholar
  32. 32.
    Obara S, McGinity JW. Influence of processing variables on the properties of free films prepared from aqueous polymeric dispersions by a spray technique. Int J Pharm. 1995;126(1–2):1–10.CrossRefGoogle Scholar
  33. 33.
    Brock D, Zeitler JA, Funke A, Knop K, Kleinebudde P. A comparison of quality control methods for active coating processes. Int J Pharm. 2012;439(1–2):289–95.PubMedCrossRefGoogle Scholar
  34. 34.
    Ho L, Müller R, Krüger C, Gordon KC, Kleinebudde P, Pepper M, et al. Investigating dissolution performance critical areas on coated tablets: a case study using terahertz pulsed imaging. J Pharm Sci. 2010;99(1):392–402.PubMedCrossRefGoogle Scholar
  35. 35.
    Roy A, Ghosh A, Datta S, Das S, Mohanraj P, Deb J, et al. Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets. Saudi Pharm J. 2009;17(3):233–41.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Zeitler JA, Shen Y, Baker C, Taday PF, Pepper M, Rades T. Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging. J Pharm Sci. 2007;96(2):330–40.PubMedCrossRefGoogle Scholar
  37. 37.
    Ervasti T, Silfsten P, Ketolainen J, Peiponen K-E. A study on the resolution of a terahertz spectrometer for the assessment of the porosity of pharmaceutical tablets. Appl Spectrosc. 2012;66(3):319–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Yang QW, Flament MP, Siepmann F, Busignies V, Leclerc B, Herry C, et al. Curing of aqueous polymeric film coatings: importance of the coating level and type of plasticizer. Eur J Pharm Biopharm. 2010;74(2):362–70.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Pharmaceutical Technology R&D Laboratories; CMC CenterTakeda Pharmaceutical Company Ltd.OsakaJapan
  2. 2.Faculty of Pharmaceutical SciencesToho UniversityFunabashiJapan

Personalised recommendations