Skip to main content
SpringerLink
Log in

Chitosan and Enteric Polymer Based Once Daily Sustained Release Tablets of Aceclofenac: In Vitro and In Vivo Studies

  • Research Article/Themed Issue: Oral/Guest Editors: Stephen A. Howard and Jian-Xin Li
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug–excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. K. Parfitt. Analgesics, anti-inflammatory and antipyretics. In J. E. F. Reynolds (ed.), Martindale: The Complete Drug Reference. 32nd ed, Massachusetts, 1999, pp. 1–12.

  2. A. E. Kay, and A. Alldred. Rheumatoid arthritis and osteoarthritis. In R. Walker, and C. Edwards (eds.), Clinical Pharmacy and Therapeutics, 3rd ed., Churchill Livingstone, London, UK, 2003, pp. 791–807.

    Google Scholar 

  3. A. C. Moffet, M. D. Osselton, B. Widdop. Clarke's analysis of drugs and poisons. 3rd ed., Pharmaceutical Press, London, UK (2006).

  4. M. Y. Rao, J. K. Veni, and G. Jayasagar. Formulation and evaluation of diclofenac sodium using hydrophilic matrices. Drug. Dev. Ind. Pharm. 27:759–766 (2001).

    Article  PubMed  CAS  Google Scholar 

  5. L. Maggi, E. O. Machiste, M. L. Torre, and U. Conte. Formulation of biphasic release tablets containing slightly soluble drugs. Eur. J. Pharm. Biopharm. 48:37–42 (1999).

    Article  PubMed  CAS  Google Scholar 

  6. Y. W. Chien. Regulatory considerations in controlled release medication. In Y. W. Chien (ed.), Novel Drug Delivery Systems, Marcel Dekker, New York, NY, 1982, pp. 577–578.

    Google Scholar 

  7. S. Mutalik, A. Naha, A. N. Usha et al. Preparation, in vitro, Preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac. Arch. Pharm. Res. 30:222–234 (2007).

    Article  PubMed  CAS  Google Scholar 

  8. M. George, and E. T. Abraham. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J. Controlled. Rel. 114:1–14 (2006).

    Article  CAS  Google Scholar 

  9. M. Fukuda, A. P. Nicholas, and J. W. McGinity. Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum. Int. J. Pharm. 310:90–100 (2006).

    Article  PubMed  CAS  Google Scholar 

  10. K. Wang, and H. Zhimin. Alginate–konjac glucomannan–chitosan beads as controlled release matrix. Int. J. Pharm. 244:117–126 (2001).

    Article  Google Scholar 

  11. R. Barreiro-Iglesias, R. Coronilla, A. Concheiro, and C. Alvarez-Lorenzo. Preparation of chitosan beads by simultaneous cross-linking/insolubilisation in basic pH. Rheological optimisation and drug loading/release behaviour. Eur. J. Pharm. Sci. 24:77–84 (2005).

    Article  PubMed  CAS  Google Scholar 

  12. J. Akbua. Use of chitosonium malate as a matrix in sustained-release tablets. Int. J. Pharm. 89:19–24 (1993).

    Article  Google Scholar 

  13. J. Knapczyk. Antimycotic buccal and vaginal tablets with chitosan. Int. J. Pharm. 88:9–14 (1992).

    Article  CAS  Google Scholar 

  14. K. R. Reddy, S. Mutalik, and S. Reddy. Once-daily sustained-release matrix tablets of nicorandil: formulation and in vitro evaluation. AAPS PharmSciTech. 4:E61 (2003).

    Article  PubMed  Google Scholar 

  15. A. M. Agrawal, S. H. Neau, and P. L. Bonate. Wet granulation fine particle ethylcellulose tablets: effect of production variables and mathematical modeling of drug release. AAPS PharmSci. 2:Article 13 (2003).

    Google Scholar 

  16. R. Chen, H. Takahashi, H. Okamoto, and K. Danjo. Particle design of three-component system for sustained release using a 4-fluid nozzle spray-drying technique. Chem. Pharm. Bull. 11:1486–1490 (2006).

    Article  Google Scholar 

  17. C. M. Silva, A. J. Ribeiro, D. Ferreira, and F. Veiga. Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation. Eur. J. Pharm. Sci. 2:148–159 (2006).

    Article  CAS  Google Scholar 

  18. M. E. Aulton, and T. I. Wells. Pharmaceutics-The Science of Dosage Form Design. Churchill Livingstone, London, UK, (1988).

  19. Indian Pharmacopoeia. Ministry of Health and Family Welfare. Government of India, Vol 2, Delhi, India: Controller of Publication; 1996.

  20. B. V. Joshi, V. B. Patil, and V. B. Pokharkar. Compatibility studies between carbamazepine and tablet excipients using thermal and non-thermal methods. Drug Dev. Ind. Pharm. 6:687–694 (2002).

    Article  Google Scholar 

  21. H. A. Kibbe. Hand Book of Pharmaceutical Excipients. 3rd ed. American pharmaceutical association, Pharmaceutical press, London, (2000).

  22. J. A. Seitz, S. P. Mehta, and J. L. Yeager. Tablet coating. In L. Lachman, H. A. Liberman, and J. L. Kanig (eds.), The Theory and Practice of Industrial Pharmacy, 3rd ed., Varghese Publishing House, Delhi, India, 1987, pp. 346–373.

    Google Scholar 

  23. U. V. Banakar. Dissolution of modified release dosage forms. In J. Swarbrick (ed.), Pharmaceutical Dissolution Testing, Marcel Dekker, New York, NY, 1992, pp. 299–312.

    Google Scholar 

  24. G. F. Palmieri, S. Michelini, P. D. Martino, and S. Martelli. Polymers with pH-dependent solubility: possibility of use in the formulation of gastro resistant and controlled-release matrix tablets. Drug Dev Ind Pharm. 26:837–845 (2000).

    Article  PubMed  CAS  Google Scholar 

  25. C. Yomota, T. Miyazaki, and S. Okada. Sustained-release effect of the direct compressed tablet based on chitosan and Na alginate. Yakugaku Zasshi. 114:257–263 (1994).

    PubMed  CAS  Google Scholar 

  26. J. S. Grundy, K. E. Anderson, J. A. Rogers, and R. T. Foster. Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. II. Improved in vitro–in vivo correlation using a two-phase dissolution test. J. Control Release. 48:9–17 (1997).

    Article  CAS  Google Scholar 

  27. C. M. Negrin, A. Delgado, M. Llabres, and C. Evora. In vivo–in vitro study of biodegradable methadone delivery systems. Biomaterials. 22:563–570 (2001).

    Article  PubMed  CAS  Google Scholar 

  28. X. Yang, G. Zhang, W. Li, B. Peng, Z. Liu, and W. Pan. Design and evaluation of Jingzhiguanxin monolithic osmotic pump tablet. Chem. Pharm. Bull. 4:465–469 (2006).

    Article  Google Scholar 

Download references

Acknowledgements

Authors are thankful to Lupin Research Park, Pune, India for the gift samples of aceclofenac and other excipients. They are grateful to Dr. K. Narayana Prabhu, Asst Professor, NITK, Suratkal for his kind help and co-operation in SEM studies.

Author information

Authors and Affiliations

  1. Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India

    Srinivas Mutalik, Krishnan Manoj, Meka Sreenivasa Reddy, Achutha Nayak Usha, Parambil Anju, Averineni Kumar Ranjith & Nayanabhirama Udupa

  2. Department of OBG, Kasturba Medical College, Manipal University, Manipal, 576104, Karnataka, India

    Pralhad Kushtagi

  3. School of Pharmacy, University of Queensland, St. Lucia, Brisbane, QLD, 4072, Australia

    Srinivas Mutalik

Authors
  1. Srinivas Mutalik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krishnan Manoj
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meka Sreenivasa Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pralhad Kushtagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Achutha Nayak Usha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Parambil Anju
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Averineni Kumar Ranjith
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nayanabhirama Udupa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srinivas Mutalik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mutalik, S., Manoj, K., Reddy, M.S. et al. Chitosan and Enteric Polymer Based Once Daily Sustained Release Tablets of Aceclofenac: In Vitro and In Vivo Studies. AAPS PharmSciTech 9, 651–659 (2008). https://doi.org/10.1208/s12249-008-9075-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-008-9075-3

Key words

Search

Navigation