Skip to main content
Log in

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Theeuwes F. Oros osmotic system development.Drug Dev Ind Pharm. 1983;9:1331–1357.

    Article  CAS  Google Scholar 

  2. Ahuja S.Analytical Profiles of Drug Substances and Excipients. London, UK: Academic Press; 1985:527–548.

    Google Scholar 

  3. Merino M, Peris RJ, Torres MF, Sanchez PA, Carbonell MC, Casabo VG. Evidence of a specialized transport mechanism for the intestinal absorption of baclofen.Biopharm Drug Dispos. 1989;10:279–297.

    Article  PubMed  CAS  Google Scholar 

  4. Cejudo-Ferragud E, Nácher A, Polache A, Cercós-Fortea T, Merino MC, Casabó VG. Evidence of competitive inhibition for the intestinal absorption of baclofen for phenylalanine.Int J Pharm. 1996;132:63–69.

    Article  CAS  Google Scholar 

  5. Hugenholtz H, Nelson RF, Dehoux E. Intrathecal baclofen: the importance of catheter position.Can J Neurol Sci. 1993;20:165–170.

    PubMed  CAS  Google Scholar 

  6. Martindale.Martindale: The Complete Drug Reference. Chicago, IL: Pharmaceutical Press; 2005:1758–1759.

    Google Scholar 

  7. Contin M, Riva R, Albani F, Baruzzi A. Pharmacokinetic optimization in the treatment of Parkinson’s disease.Clin Pharmacokinet. 1996;30:463–481.

    Article  PubMed  CAS  Google Scholar 

  8. Erni W, Held K. The hydrodynamically balanced system: a novel principle of controlled drug release.Eur Neurol. 1987;27:21–27.

    Article  PubMed  CAS  Google Scholar 

  9. Dempski RE, Scholtz EC, Oberholtzer ER, Yeh KC. Pharmaceutical design and development of a Sinemit controlled release formulation.Neurology. 1989;39:20–24.

    Article  PubMed  CAS  Google Scholar 

  10. Yeh KC, August TF, Bush DF. Pharmacokinetics and bioavailability of Sinemit CR: a summary of human studies.Neurology. 1989;39:25–38.

    PubMed  CAS  Google Scholar 

  11. LeWitt PA, Nelson MV, Berchou RC. Controlled-release carbidopa/levodopa (Sinemit 50/200 CR4): clinical and pharmacokinetic studies.Neurology. 1989;39:45–53.

    PubMed  CAS  Google Scholar 

  12. Crevoisier C, Hoevels B, Zürcher G, Da Prada M. Bioavailability of 1-dopa after Madopar HBS administration in healthy volunteers.Eur Neurol. 1987;27:36–46.

    Article  PubMed  CAS  Google Scholar 

  13. Marion MH, Stocchi F, Malcolm SL, Quinn NP, Jenner P, Marsden CD. Single-dose studies of a slow-release preparation of levodopa and benserazide (Madopar HBS) in Parkinson’s disease.Eur Neurol. 1987;27:54–58.

    Article  PubMed  Google Scholar 

  14. Cruaud O, Benita S, Benoit JP. The characterization and release kinetics evaluation of baclofen microspheres designed for intrathecal injection.Int J Pharm. 1999;177:247–257.

    Article  PubMed  CAS  Google Scholar 

  15. Lagarce F, Renaud P, Faisnat N, et al. Baclofen-loaded microspheres: preparation and efficacy testing in a new rabbit model.Eur J Pharm Biopharm. 2005;59:449–459.

    Article  PubMed  CAS  Google Scholar 

  16. Zierski J, Muller H, Dralle D, Wurdinger T. Implanted pump systems for treatment of spasticity.Acta Neurochir Suppl (Wien). 1988;43:94–99.

    CAS  Google Scholar 

  17. Loubser PG, Narayan RK, Sandin KJ, Donovan WH, Russell KD. Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury.Paraplegia. 1991;29:48–64.

    PubMed  CAS  Google Scholar 

  18. Hugenholtz H, Nelson RF, Dehoux E, Birkerton R. Intrathecal baclofen for intractable spinal spasticity—a double-blind cross-over comparison of 6 patients.Can J Neurol Sci. 1992;19:188–195.

    PubMed  CAS  Google Scholar 

  19. Hugenholtz H, Nelson RF, Dehoux E. Intrathecal baclofen: the importance of catheter position.Can J Neurol Sci. 1993;20:165–167.

    PubMed  CAS  Google Scholar 

  20. Ritger PL, Peppas NA. A simple equation for description of solute release, II: Fickian and anomalous release from swellable devices.J Control Release. 1987;5:37–42.

    Article  CAS  Google Scholar 

  21. Sato H, Miyagawa Y, Okabe T, Miyajima M, Sunada H. Dissolution mechanism of diclofenac sodium from wax matrix granules.J Pharm Sci. 1997;86:929–934.

    Article  PubMed  CAS  Google Scholar 

  22. Raghuram RK, Srinivas M, Srinivas R. Once-daily sustained-release matrix tablets of nicorandil: formulation and in vitro evaluation.AAPS PharmSciTech [serial online]. 2003;4:E61.

  23. Lachman L, Lieberman HA, Kanig JL.The Theory and Practice of Industrial Pharmacy. Philadelphia, PA: Lea and Febiger; 1987:317–318.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers.Pharm Acta Helv. 1985;60:110–112.

    PubMed  CAS  Google Scholar 

  26. Peppas NA, Sahlin JJ. A simple equation for the description of solute release, III: coupling of diffusion and relaxation.Int J Pharm. 1989;57:169–175.

    Article  CAS  Google Scholar 

  27. 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 of slabs, spheres, cylinders or discs.J Control Release. 1987;5:23–35.

    Article  CAS  Google Scholar 

  28. Talukdar MM, Rommbaut P, Kinget R. Comparative study on xanthan gum and hydroxypropyl methylcellulose as matrices for controlled-release drug delivery.Int J Pharm. 1996;129:233–241.

    Article  CAS  Google Scholar 

  29. Reza MS, Abdul Quadir M, Haider SS. Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for controlled-release drug delivery.J Pharm Pharm Sci. 2003;6:282–291.

    PubMed  CAS  Google Scholar 

  30. Mockel JE, Lippold BC. Zero-order release from hydrocolloid Matrices.Pharm Res. 1993;10:1066–1070.

    Article  PubMed  CAS  Google Scholar 

  31. Pharmaceutical Codex.Principles and Practice of Pharmaceutics. London, UK: Pharmaceutical Press; 1994:178–186.

    Google Scholar 

  32. O’Neil MJ, ed.The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co; 2001:164–165.

    Google Scholar 

  33. Martin A, ed. Micromeritics. In:Physical Pharmacy. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:423–454.

    Google Scholar 

  34. Alderman DA. A review of cellulose ethers in hydrophilic matrices for oral controlled release dosage forms.Int J Pharm Technol Prod Manuf. 1984;5:1–9.

    CAS  Google Scholar 

  35. Khan KA, Rhodes CT. Evaluation of different viscosity grades of sodium carboxy methylcellulose as tablet disintegrants.Pharm Acta Helv. 1975;50:99–102.

    PubMed  CAS  Google Scholar 

  36. Shah NH, Lazarus JH, Jarwoski CL. Carboxy methylcellulose: effect of degree of polymerization and substitution on tablet disintegration and dissolution.J Pharm Sci. 1981;70:611–613.

    Article  PubMed  CAS  Google Scholar 

  37. Al-Hmoud H, Efentakis M, Choulis NH. A controlled release matrix using a mixture of hydrophilic and hydrophobic polymers.Int J Pharm. 1991;68:R1-R3.

    Article  Google Scholar 

  38. Esmail MN, Yousry ME, Sayed HK. Effect of accelerated storage conditions on the dissolution and bioavailability of amitriptyline from sustained-release capsules.SPJ. 1996;4:92–98.

    Google Scholar 

  39. Braco SA, Lamas MC, Salamon CJ. In-vitro studies of diclofenac sodium controlled-release from biopolymeric hydrophilic matrices.J Pharm Pharm Sci. 2002;5:213–219.

    Google Scholar 

  40. Goetz CG, Tanner CM, Carrol VS. Controlled-release Sinemet.Neurology. 1987;37:1567–1575.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hamdy Abdelkader.

Additional information

Themed Issue: Oral Controlled Release Development and Technology

Guest Editor — Stephen A. Howard and Jian-Xin Li

Published: November 30, 2007

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdelkader, H., Abdalla, O.Y. & Salem, H. Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation. AAPS PharmSciTech 8, 100 (2007). https://doi.org/10.1208/pt0804100

Download citation

  • Received:

  • Revised:

  • Accepted:

  • DOI: https://doi.org/10.1208/pt0804100

Keywords

Navigation