Advertisement

AAPS PharmSciTech

, Volume 19, Issue 3, pp 1426–1436 | Cite as

A Novel Approach for Dry Powder Coating of Pellets with Ethylcellulose. Part II: Evaluation of Caffeine Release

  • Beatrice Albertini
  • Cecilia Melegari
  • Serena Bertoni
  • Luisa Stella Dolci
  • Nadia Passerini
Research Article
  • 164 Downloads

Abstract

The objective of this study was to assess the efficacy and the capability of a novel ethylcellulose-based dry-coating system to obtain prolonged and stable release profiles of caffeine-loaded pellets. Lauric and oleic acids at a suitable proportion were used to plasticize ethylcellulose. The effect of coating level, percentage of drug loading, inert core particle size, and composition of the coating formulation including the anti-sticking agent on the drug release profile were fully investigated. A coating level of 15% w/w was the maximum layered amount which could modify the drug release. The best controlled drug release was obtained by atomizing talc (2.5% w/w) together with the solid plasticizer during the dry powder-coating process. SEM pictures revealed a substantial drug re-crystallization on the pellet surface, and the release studies evidenced that caffeine diffused through the plasticized polymer acting as pore former. Therefore, the phenomenon of caffeine migration across the coating layer had a strong influence on the permeability of the coating membrane. Comparing dry powder-coated pellets to aqueous film-coated ones, drug migration happened during storage, though more sustained release profiles were obtained. The developed dry powder-coating process enabled the production of stable caffeine sustained release pellets. Surprisingly, the release properties of the dry-coated pellets were mainly influenced by the way of addition of talc into the dry powder-coating blend and by the drug nature and affinity to the coating components. It would be interesting to study the efficacy of novel coating system using a different API.

KEY WORDS

Ethylcellulose Dry powder coating of pellets Caffeine release Drug migration Pore former 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

12249_2018_964_MOESM1_ESM.jpg (25 kb)
Fig. S1 Pictures of film coated pellets taken immediately after the film coating process (Fig. S1a) and after 1 month of storage at room conditions (Fig. S1b). (JPEG 24 kb)

References

  1. 1.
    Sauer D, Cerea M, DiNunzio J, McGinity JW. Dry powder coating of pharmaceuticals: a review. Int J Pharm. 2013;457(2):488–502.  https://doi.org/10.1016/j.ijpharm.2013.02.032.CrossRefPubMedGoogle Scholar
  2. 2.
    Foppoli A, Maroni A, Cerea M, Zema L, Gazzaniga A. Dry coating of solid dosage forms: an overview of processes and applications. Drug Dev Ind Pharm. 2017;43(12):1919–31.  https://doi.org/10.1080/03639045.2017.1355923.CrossRefPubMedGoogle Scholar
  3. 3.
    Albertini B, Bertoni S, Melegari C, Dolci LS, Passerini N. A novel approach for dry powder coating of pellets with ethylcellulose. Part I: evaluation of film formulation and process set up. Int J Pharm. 2017;516(1-2):380–91.  https://doi.org/10.1016/j.ijpharm.2016.11.054.CrossRefPubMedGoogle Scholar
  4. 4.
    Obara S, Maruyama N, Nishiyama Y, Kokubo H. Dry coating: an innovative enteric coating method using a cellulose derivative. Eur J Pharm Biopharm. 1999;47(1):51–9.  https://doi.org/10.1016/S0939-6411(98)00087-3.CrossRefPubMedGoogle Scholar
  5. 5.
    Pearnchob N, Bodmeier R. Coating of pellets with micronized ethylcellulose particles by a dry powder coating technique. Int J Pharm. 2003;268(1-2):1–11.  https://doi.org/10.1016/j.ijpharm.2003.07.012.CrossRefPubMedGoogle Scholar
  6. 6.
    Pearnchob N, Bodmeier R. Dry polymer powder coating and comparison with conventional liquid-based coatings for Eudragit® RS, ethylcellulose and shellac. Eur J Pharm Biopharm. 2003;56(3):363–9.  https://doi.org/10.1016/S0939-6411(03)00121-8.CrossRefPubMedGoogle Scholar
  7. 7.
    Pearnchob N, Bodmeier R. Dry powder coating of pellets with micronized Eudragit® RS for extended drug release. Pharm Res. 2003;20(12):1970–6.  https://doi.org/10.1023/B:PHAM.0000008044.78968.81.CrossRefPubMedGoogle Scholar
  8. 8.
    Kablitz CD, Harder K, Urbanetz NA. Dry coating in a rotary fluid bed. Eur J Pharm Sci. 2006;27(2-3):212–9.  https://doi.org/10.1016/j.ejps.2005.10.001.CrossRefPubMedGoogle Scholar
  9. 9.
    Kablitz CD, Urbanetz NA. Stability of dry coated solid dosage forms. Pharm Dev Technol. 2009;14(6):613–22.  https://doi.org/10.3109/10837450902882336.CrossRefPubMedGoogle Scholar
  10. 10.
    Cerea M, Foppoli A, Maroni A, Palugan L, Zema L, Sangalli ME. Dry coating of soft gelatin capsules with HPMCAS. Drug Dev Ind Pharm. 2008;34(11):1196–200.  https://doi.org/10.1080/03639040801974360.CrossRefPubMedGoogle Scholar
  11. 11.
    Cao QR, Liu Y, Xu WJ, Lee BJ, Yang M, Cui JH. Enhanced oral bioavailability of novel muco-adhesive pellets containing valsartan prepared by a dry powder-coating technique. Int J Pharm. 2012;343:325–33.CrossRefGoogle Scholar
  12. 12.
    Park HJ, Lee GH, Jun JH, Son M, Choi YS, Choi MK, et al. Formulation and in vivo evaluation of probiotics-encapsulated pellets with hydroxypropyl methylcellulose acetate succinate (HPMCAS). Carbohydr Polym. 2016;20:136–692.Google Scholar
  13. 13.
    Cerea M, Zheng W, Young CR, McGinity JW. A novel powder coating process for attaining taste masking and moisture protective films applied to tablets. Int J Pharm. 2004;279(1-2):127–39.  https://doi.org/10.1016/j.ijpharm.2004.04.015.CrossRefPubMedGoogle Scholar
  14. 14.
    Zheng W, Cerea M, Sauer D, McGinity JW. Properties of theophylline tablets powder-coated with methacrylate ester copolymers. J Drug Del Sci Technol. 2004;14(4):319–25.  https://doi.org/10.1016/S1773-2247(04)50054-0.CrossRefGoogle Scholar
  15. 15.
    Sauer D, McGinity JW. Properties of theophylline tablets dry powder coated with Eudragit® E PO and Eudragit® L 100-55. Drug Dev Technol. 2009;14:632–341.Google Scholar
  16. 16.
    Melegari C, Bertoni S, Genovesi A, Hughes K, Rajabi-Siahboomi AR, Passerini N. Ethylcellulose film coating of guaifenesin-loaded pellets: a comprehensive evaluation of the manufacturing process to prevent drug migration. Eur J Pharm Biopharm. 2016;100:15–26.  https://doi.org/10.1016/j.ejpb.2015.12.001.CrossRefPubMedGoogle Scholar
  17. 17.
    Fernández-Pérez M, Villafranca-Sánchez M, Flores-Céspedes F, Daza-Fernández I. Ethylcellulose and lignin as bearer polymers in controlled release formulations of chloridazon. Carbohydr Polym. 2011;83(4):1672–9.  https://doi.org/10.1016/j.carbpol.2010.10.024.CrossRefGoogle Scholar
  18. 18.
    Rege B-D, Gawel J, Kou JH. Identification of critical process variables for coating actives onto tablets via statically designed experiments. Int J Pharm. 2002;237(1-2):87–94.  https://doi.org/10.1016/S0378-5173(02)00037-6.CrossRefPubMedGoogle Scholar
  19. 19.
    Moes JJ, Ruijken M-M, Gout E, Frijlink HW, Ugwoke MI. Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity, content uniformity and coating thickness measurements. Int J Pharm. 2008;357(1-2):108–18.  https://doi.org/10.1016/j.ijpharm.2008.01.062.CrossRefPubMedGoogle Scholar
  20. 20.
    Brock D, Zeitler JA, Funke A, Knop K, Kleinebudde P. Evaluation of critical process parameters for inter-tablet coating uniformity of active-coated GITS using terahertz pulsed imaging. Eur J Pharm Biopharm. 2014;88(2):434–42.  https://doi.org/10.1016/j.ejpb.2014.06.016.CrossRefPubMedGoogle Scholar
  21. 21.
    Siepmann J, Siepmann F, Paeratakul O, Bodmeier R. Process and formulation factors affecting drug release from pellets coated with ethylcellulose Pseudolatex Aquacoat. In: Felton L-A, McGinity JW, editors. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, vol. 176. 3rd ed. New York: Drug and Pharmaceutical Sciences. Informa Healthcare. USA Inc; 2008. p. 203–35.Google Scholar
  22. 22.
    Li G, Ha D, Guan T, Zhao X, He H, Tang X. Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double layer coating for reducing 5-ISMN migration and sublimation. Int J Pharm. 2010;400(1-2):138–44.  https://doi.org/10.1016/j.ijpharm.2010.08.046.CrossRefPubMedGoogle Scholar
  23. 23.
    Nikowitz K, Pintye-Hódi K, Regdon G Jr. Study of the recrystallization in coated pellets – effect of coating on API crystallinity. Eur J Pharm Sci. 2013;48(3):563–71.  https://doi.org/10.1016/j.ejps.2012.12.018.CrossRefPubMedGoogle Scholar
  24. 24.
  25. 25.
    Monteyne T, Vancoille J, Remon JP, Vervaet C, De Beer T. Continuous melt granulation: influence of process and formulation parameters upon granule and tablet properties. Eur J Pharm Biopharm. 2016;107:249–62.  https://doi.org/10.1016/j.ejpb.2016.07.021.CrossRefPubMedGoogle Scholar
  26. 26.
    Hubert S, Briancon S, Hedoux A, Guinet Y, Paccou L, Fessi H, et al. Process induced transformations during tablet manufacturing: phase transition analysis of caffeine using DSC and low frequency micro-Raman spectroscopy. Int J Pharm. 2011;420(1):76–83.  https://doi.org/10.1016/j.ijpharm.2011.08.028.CrossRefPubMedGoogle Scholar
  27. 27.
    Pinto SS, Diogo P. Thermochemical study of two anhydrous polymorphs of caffeine. J Chem Thermodyn. 2006;38(12):1515–22.  https://doi.org/10.1016/j.jct.2006.04.008.CrossRefGoogle Scholar
  28. 28.
    Smikalla M, Mescher A, Walzel P, Urbanetz NA. Impact of excipients on coating efficiency in dry powder coating. Int J Pharm. 2011;405(1-2):122–31.  https://doi.org/10.1016/j.ijpharm.2010.12.001.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Beatrice Albertini
    • 1
  • Cecilia Melegari
    • 1
  • Serena Bertoni
    • 1
  • Luisa Stella Dolci
    • 1
  • Nadia Passerini
    • 1
  1. 1.Department of Pharmacy and BioTechnologyUniversity of BolognaBolognaItaly

Personalised recommendations