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Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate

Abstract

The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f 2) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system.

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References

  1. Tomford WW. Chondroprotective agents in the treatment of articular cartilage degeneration.Oper Tech Sports Med. 2000;8:120–121.

    Article  Google Scholar 

  2. Uebelhart D, Thonar EJ, Delmas PD, et al. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study.Osteoarthrit Cartil. 1998;6:39–46.

    Article  Google Scholar 

  3. Pipitone VR. Chondroprotection with chondroitin sulfate.Drugs Exp Clin Res. 1991;17:3–7.

    PubMed  CAS  Google Scholar 

  4. Ronca F, Palmieri L, Panicucci P, Ronca G. Anti-inflammatory activity of chondroitin sulfate.Osteoarthrit Cartil. 1998;6:14–21.

    Article  Google Scholar 

  5. Colombo P. Swelling-controlled release in hydrogel matrices for oral route.Adv Drug Del Rev. 1993;11:37–57.

    Article  CAS  Google Scholar 

  6. Siepmann J, Kranz H, Bodmeier R, Peppas NA. HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics.Pharm Res. 1999;16:1748–1756.

    PubMed  Article  CAS  Google Scholar 

  7. Colombo P, Bettini R, Santi P, Peppas NA. Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance.Pharm Sci Technol Today. 2000;3:198–204.

    PubMed  Article  CAS  Google Scholar 

  8. Kiil S, Dam JK. Controlled drug delivery from swellable hydroxypropylmethylcellulose matrices: model-based analysis of observed radial front movements.J Control Release. 2003;90:1–21.

    PubMed  Article  CAS  Google Scholar 

  9. Ford J, Rubinstein M, Hogan J. Propranolol hydrochloride and aminophylline release from matrix tablet containing hydroxypropyl methylcellulose.Int J Pharm. 1985;24:339–350.

    Article  CAS  Google Scholar 

  10. Narasimhan B, Peppas NA. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier.J Pharm Sci. 1997;86:297–304.

    PubMed  Article  Google Scholar 

  11. Zhang L, Li N, Zhao F, Li K. Spectroscopic study on the interaction between methylene blue and chondroitin 4-sulphate and its analytical application.Ana Sci. 2004;20:445–450.

    Article  CAS  Google Scholar 

  12. Lopes CM, Lobo JMS, Costa P, Pinto JF. Directly compressed mini matrix tablets containing ibuprofen: preparation and evaluation of sustained release.Drug Dev Ind Pharm. 2006;32:95–106.

    PubMed  Article  CAS  Google Scholar 

  13. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles.Eur J Pharm Sci. 2001;13:123–133.

    PubMed  Article  CAS  Google Scholar 

  14. Ritger PL, Peppas NA. A simple equation for description of solute release. I. Fickian and non-fickian release from non-swellable devices in the form slabs, spheres, cylinder or discs.J Control Release. 1987;5:23–36.

    Article  CAS  Google Scholar 

  15. Donbrow M, Samuelov Y. Zero order drug delivery from double-layer porous films: release rate profiles from ethyl cellulose and polyethylene glycol mixtures.J Pharm Pharmacol. 1980;32:463–470.

    PubMed  CAS  Google Scholar 

  16. Higuchi T. Rate of release of medicament from ointment bases containing drugs in suspension.J Pharm Sci. 1961;50:874–875.

    PubMed  Article  CAS  Google Scholar 

  17. Higuchi T. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices.J Pharm Sci. 1963;52:1145–1149.

    PubMed  Article  CAS  Google Scholar 

  18. Korsmeyer RW, Gumy R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers.Int J Pharm. 1983;15:25–35.

    Article  CAS  Google Scholar 

  19. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers.Pharm Acta Helv. 1985;60:110–111.

    PubMed  CAS  Google Scholar 

  20. Bolton S, Bon C.Pharmaceutical Statistics: Practical and Clinical Applications. New York, NY: Marcel Dekker; 2004.

    Google Scholar 

  21. Papadimitriou E, Buckton G, Efentakis M. Probing the mechanisms of swelling of hydroxypropyl methylcellulose matrices.Int J Pharm. 1993;98:57–62.

    Article  CAS  Google Scholar 

  22. Melia CD. Hydrophilic matrix sustained release systems based on polysaccharide carriers.Crit Rev Ther Drug Carrier Syst. 1991;8:395–421.

    PubMed  CAS  Google Scholar 

  23. Rowe RC, Sheskey RJ, Weller PJ.Handbook of Pharmaceutical Excipients. London, UK: Pharmaceutical Press; 2003.

    Google Scholar 

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Correspondence to Amelia Avachat.

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Published: October 19, 2007

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Avachat, A., Kotwal, V. Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate. AAPS PharmSciTech 8, 51–56 (2007). https://doi.org/10.1208/pt0804088

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  • DOI: https://doi.org/10.1208/pt0804088

Keywords

  • Chondroitin sulphate
  • diclofenac sodium
  • hydroxypropylmethylcellulose
  • controlled release