Development and In Vitro Evaluation of a Novel Pulsatile Drug Delivery System Containing Dexketoprofen Trometamol

Abstract

Purpose

A pulsatile drug delivery system containing dexketoprofen trometamol was designed by combining immediate release and colon-targeted mini tablets into a capsule.

Methods

Both immediate release and colon-targeted mini tablets were prepared by wet granulation. Furthermore, colon-targeted mini tablets were coated with Eudragit L 100, Eudragit S 100, Eudragit RS 30D, and ethylcellulose (Surelease®) using Wurster and pan coating methods.

Results

The optimum drug release of the system developed in the study was found to be mini tablets coated with 30% Eudragit S 100 on a 20% Surelease® subcoating for the purpose of colon targeting.

Conclusion

In the finished product, the immediate release part released the drug within the first hour, and less than 5% release was observed from the colon-targeted tablets in a 0.1 N HCl in 2 h. Then, less than 20% release occurred in the colon-targeted tablets up to 6 h in pH 6.8 phosphate buffer solution. The cumulative release rate reached 100% for up to 12 h. To our knowledge, it was the first time dexketoprofen trometamol was designed by combining both immediate release and colon-targeted mini tablets in a one dosage form.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  1. 1.

    Keerthi ML, Kiran RS, Rao VUM, Sannapu A, Dutt AG, Krishna KS. Pharmaceutical mini-tablets, its advantages, formulation possibilities and general evaluation aspects: a review. Int. J. Pharm. Sci. Rev. Res. 2014;28(1):214–21.

    Google Scholar 

  2. 2.

    Lopes CM, Lobo JMS, Pinto JF, Costa P. Compressed mini-tablets as a biphasic delivery system. Int. J. Pharm. 2006;323:93–100.

    CAS  Article  Google Scholar 

  3. 3.

    Das S, Deshmukh R, Jha A. Role of natural polymers in the development of multiparticulate systems for colon drug targeting. Syst Rev Pharmacy. 2010;1(1):79–85.

    Article  Google Scholar 

  4. 4.

    Chourasia MK, Jain SK. Design and development of multiparticulate system for targeted drug delivery to colon. Drug Deliv. 2004;11(3):201–7.

    CAS  Article  Google Scholar 

  5. 5.

    Kibria G, Ul-Jalil R. The effect of the ratio of two acrylic polymers on the in vitro release kinetics of ketoprofen from pellets prepared by extrusion and spheronisation technique. Pak. J. Pharm. Sci. 2008;21(2):92–7.

    CAS  PubMed  Google Scholar 

  6. 6.

    Miranda HF, Sierralta F, Aranda N, Noriega V, Prieto JC. Pharmacological profile of dexketoprofen in orofacial pain. Pharmacol. Rep. 2016;68:1111–6.

    CAS  Article  Google Scholar 

  7. 7.

    Barbanoj MJ, Antonijoan RM, Gich I. Clinical pharmacokinetics of dexketoprofen. Clin Pharmacokinet. 2001;40(4):245–62.

    CAS  Article  Google Scholar 

  8. 8.

    Garcia-Arieta A, Gordon J, Gwaza L, Mangas-Sanjuan V, Álvarez C, Torrado JJ. Agitation rate and time for complete dissolution in bcs biowaivers based on investigation of a BCS biowaiver for dexketoprofen tablets. Mol. Pharmaceutics. 2015;12:3194–201.

    CAS  Article  Google Scholar 

  9. 9.

    Rudolph MW, Klein S, Beckert TE, Petereit HU, Dressman JB. A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis. Eur. J. Pharm. Biopharm. 2001;51:183–90.

    CAS  Article  Google Scholar 

  10. 10.

    Patel HP, Karwa P, Patel NJ. A novel approach to sustained Zolpidem tartrate release: Compressed mini-tablets. Int. J. Pharm. Sci. Rev. and Res. 2011;7(2):53–8.

    CAS  Google Scholar 

  11. 11.

    Aleksovski A, Luštrik M, Šibanc R, Dreu R. Design and evaluation of a specific, bi-phase extended release system based on differently coated mini-tablets. Eur. J. Pharm. Sci. 2015;75:114–22.

    CAS  Article  Google Scholar 

  12. 12.

    Stubbe BG, De Smedt SC, Demeester J. “Programmed polymeric devices”for pulsed drug delivery. Pharm. Res. 2004;21:1732–40.

    CAS  Article  Google Scholar 

  13. 13.

    Gupta VK, Gnanarajan G, Kothiyal P. A review article on colonic targeted drug delivery system. The Pharma Innov. 2012;1(7):14–24.

    CAS  Google Scholar 

  14. 14.

    Ghugarkar P, Kulat P, Swain K, Suggala V, Shaik D. Colon targeted drug delivery system: a review on primary and novel approaches. Int. J. Pharm. Sci. Res. 2015;6(7):2681–8.

    CAS  Google Scholar 

  15. 15.

    Kumar P, Mishra B. Colon targeted drug delivery systems -an overview. Curr. Drug Deliv. 2008;5:186–98.

    CAS  Article  Google Scholar 

  16. 16.

    Krishnamachari Y, Madan P, Lin S. Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon. Int. J. Pharm. 2007;338:238–47.

    CAS  Article  Google Scholar 

  17. 17.

    Yang L, Chu JS, Fix JA. Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation. Int. J. Pharm. 2002;235:1–15.

    CAS  Article  Google Scholar 

  18. 18.

    Ibekwe VC, Fadda HM, McConnell EL, Khela MK, Evans DF, Basit AW. Interplay between intestinal pH, transit time and feed status on the in vivo performance of pH responsive ileo-colonic release systems. Pharm Res. 2008;25(8):1828–35.

    CAS  Article  Google Scholar 

  19. 19.

    Ibekwe VC, Fadda HM, Parsons GE, Basit AW. A comparative in vitro assessment of the drug release performance of pH-responsive polymers for ileo-colonic delivery. Int. J. Pharm. 2006;308:52–60.

    CAS  Article  Google Scholar 

  20. 20.

    Leopold CS, Eikeler D. Eudragit E as coating material for the pH-controlled drug release in the topical treatment of inflammatory bowel disease (IBD). J Drug Target. 1998;6(2):85–94.

    CAS  Article  Google Scholar 

  21. 21.

    Patra N, Priya R, Swain S, Jena GK, Panigrahi KC, Ghose D. Pharmaceutical significance of Eudragit: A review. Future J. Pharm. Sci. 2017;3:33–45.

    Article  Google Scholar 

  22. 22.

    McConnell EL, Short MD, Basit AW. An in vivo comparison of intestinal pH and bacteria as physiological trigger mechanisms for colonic targeting in man. J. Control. Release. 2008;130(2):154–60.

    CAS  Article  Google Scholar 

  23. 23.

    Colorcon Limited. Surelease® Ethylcellulose Dispersion Type B NF. [accessed 2018 July 17]. https://www.colorcon.com/products-formulation/all-products/film-coatings/sustained-release/surelease.

  24. 24.

    Leuva VR, Patel BG, Chaudhary DJ, Patel JN, Modasiya MMK. Oral colon-specific drug delivery system. J Pharm Res. 2012;5(4):2293–7.

    Google Scholar 

  25. 25.

    Biswall PK, Kumar A, Bhadouriya AS. Design and evolution of colon specific drug delivery system. Int. J. Pharmaceut. Chem. Biol. Sc. 2013;3(1):150–67.

    Google Scholar 

  26. 26.

    U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for industry, dissolution testing and acceptance criteria for immediate-release solid oral dosage form drug products containing high solubility drug substances. August 2018, p 15.

  27. 27.

    United States Pharmacopeia 41, National Formulary 36, Rockville MD USA: United States Pharmacopeial Convention 2018.

  28. 28.

    Patel MM, Patel SL, Bhadani MN, Shah TJ, Amin AF. A synchronous colon-specific drug delivery system for orally administered mesalamine. Acta Pharm Sci. 2009;51:251–60.

    CAS  Google Scholar 

  29. 29.

    Modified and Immediate Release Formulations of Memantine. Patent No. US 2007/0065512 A1. Forest Laboratories, Inc.

  30. 30.

    Akhgari A, Garekani HA, Sadeghi F, Azimaie M. Statistical optimization of indomethacin pellets coated with pH-dependent methacrylic polymers for possible colonic drug delivery. Int. J. Pharm. 2005;305:22–30.

    CAS  Article  Google Scholar 

  31. 31.

    Forest Laboratories, Inc. Modified and Immediate Release Formulations of Memantine. United States Patents, US 2007/0065512 A1.

  32. 32.

    Patel MM, Shah TJ, Amin AF, Shah NN. Design, development, and optimization of a novel time and pH-dependent colon targeted drug delivery system. Pharm Dev Technol. 2009;14:62–9.

    CAS  PubMed  Google Scholar 

  33. 33.

    Patel MM, Amin AF. Design and optimization of colon-targeted system of theophylline for chronotherapy of nocturnal asthma. J. Pharm. Sci. 2011;100(5):1760–72.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This research was supported by DEVA Holding, Turkey.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Timucin Ugurlu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ugurlu, T., Ilhan, E. Development and In Vitro Evaluation of a Novel Pulsatile Drug Delivery System Containing Dexketoprofen Trometamol. J Pharm Innov (2020). https://doi.org/10.1007/s12247-020-09452-2

Download citation

Keywords

  • Dexketoprofen trometamol
  • Mini tablet
  • Colon targeting
  • Chronotherapy
  • Rheumatoid arthritis
  • Pulsatile release