Advertisement

AAPS PharmSciTech

, 8:167 | Cite as

Design and study of lamivudine oral controlled release tablets

  • Punna Rao Ravi
  • Sindhura Ganga
  • Ranendra Narayan Saha
Article

Abstract

The objective of this study was to design oral controlled release matrix tablets of lamivudine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, and compression force on the in vitro release of drug. In vitro release studies were performed using US Pharmacopeia type 1 apparatus (basket method) in 900 mL of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using the zero-order model equation, Higuchi’s square-root equation, and the Ritger-Peppas empirical equation. Compatibility of the drug with various excipients was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 60% HPMC 4000 cps were found to show good initial release (26% in first hour) and extended the release up to 16 hours. Matrix tablets containing 80% HPMC 4000 cps and 60% HPMC 15 000 cps showed a first-hour release of 22% but extended the release up to 20 hours. Methematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of lamivudine, with good initial release (20%–25% in first hour) and extension of release up to 16 to 20 hours, can overcome the disadvantages of conventional tablets of lamivudine.

Keywords

Controlled release matrix tablets hydroxypropyl methylcellulose lamivudine 

References

  1. 1.
    Chien YW. Novel drug delivery systems. In: Chien YW, ed.Oral Drug Delivery and Delivery Systems. New York, NY: Marcel Dekker; 1992:139–196.Google Scholar
  2. 2.
    Vyas SP, Khar RK. Controlled drug delivery: concepts and advances. In: Vyas SP, Khar RK, eds.Controlled Oral Administration. Delhi, India: Vallabh Prakashan; 2002:155–195.Google Scholar
  3. 3.
    Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO).AIDS Epidemic Update2005. Geneva, Switzerland: UNAIDS. Available at: http://www.unaids.org/epi/2005/doc/EPIupdate2005_pdf_en/epi-update2005_en.pdf. Accessed December 10, 2006.Google Scholar
  4. 4.
    Zhou J, Paton NI, Ditangco R, et al. Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database.HIV Med. 2007;8:8–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Castillo SA, Hernandez JE, Brothers CH. Long-term safety and tolerability of the lamivudine/abacavir combination as components of highly active antiretroviral therapy.Drug Saf. 2006;29:811–826.PubMedCrossRefGoogle Scholar
  6. 6.
    Anthony SF, Clifford HL. Human immunodeficiency virus (HIV) disease: AIDS and related disorders. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds.Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill; 2001:1852–1913.Google Scholar
  7. 7.
    Betty JD. Human immunodeficiency virus (HIV)—antiretroviral therapy. In: Herfindal ET, Gourley DR, eds.Textbook of Therapeutics: Drug and Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:1555–1582.Google Scholar
  8. 8.
    Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity.Clin Ther. 2000;22:911–936.PubMedCrossRefGoogle Scholar
  9. 9.
    Vargas CI, Ghaly ES. Kinetic release of theophylline from hydrophilic swellable matrices.Drug Dev Ind Pharm. 1999;25:1045–1050.PubMedCrossRefGoogle Scholar
  10. 10.
    Ranga RKV, Padmalatha DK, Buri B. Cellulose matrices for zero-order release of soluble drugs.Drug Dev Ind Pharm. 1988;14:2299–2320.CrossRefGoogle Scholar
  11. 11.
    Parojcic J, Duric Z, Jovanovic M, Ibric S. An investigation into the factors influencing drug release from hydrophilic matrix tablets based on novel carbomer polymers.Drug Deliv. 2004;11:59–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Korsenmeyer RW, Peppas NA. Macromolecular and modeling aspects of swelling-controlled systems. In: Mansdorf SZ, Roseman TJ, eds.Controlled Release Delivery Systems. New York, NY: Marcel Dekker; 1983:77.Google Scholar
  13. 13.
    Bravo SA, Lamas MC, Salomon CJ. Swellable matrices for the controlled-release of diclofenac sodium: formulation and in vitro studies.Pharm Dev Technol. 2004;9:75–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Velasco MV, Ford JL, Rowe P, Rajabi-Siahboomi AR. Influence of drug:hydroxypropyl methylcellulose ratio, drug and polymer particle size and compression force on the release of diclofenac sodium from HPMC matrices.J Control Release. 1999;57:75–85.PubMedCrossRefGoogle Scholar
  15. 15.
    Heng PWS, Chan LW, Easterbrook MG, Li X. Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets.J Control Release. 2001;76:39–49.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee BJ, Ryu SG, Cui JH. Formulation and release characteristics of hydroxypropyl methylcellulose matrix tablet containing melatonin.Drug Dev Ind Pharm. 1999;25:493–501.PubMedCrossRefGoogle Scholar
  17. 17.
    Katzhendler I, Mader K, Friedman M. Structure and hydration properties of hydroxypropyl methylcellulose matrices containing naproxen and naproxen sodium.Int J Pharm. 2000;200:161–179.PubMedCrossRefGoogle Scholar
  18. 18.
    Tapia-Albarran M, Villafuerte-Robles L. Effect of formulation and process variables on the release behavior of amoxicillin matrix tablets.Drug Dev Ind Pharm. 2004;30:901–908.PubMedCrossRefGoogle Scholar
  19. 19.
    Narasimhan B, Peppas NA. Disentanglement and repetition during dissolution of rubbery polymers.J Polym Sci Part B: Polym Phys. 1996;34:947–961.CrossRefGoogle Scholar
  20. 20.
    Narasimhan B, Peppas NA. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier.J Pharm Sci. 1997;86:297–304.PubMedCrossRefGoogle Scholar
  21. 21.
    Vazquez MJ, Perez-Marcos B, Gomez-Amoza JL, Martinez-Pacheco R, Souto C, Concheiro A. Influence of technological variables on release of drugs from hydrophilic matrices.Drug Dev Ind Pharm. 1992;8:1355–1375.CrossRefGoogle Scholar
  22. 22.
    Li S, Shen Y, Li W, Hao X. A common profile for polymer-based controlled release and its logical interpretation to general release process.J Pharm Pharm Sci. 2006;9:238–244.PubMedGoogle Scholar
  23. 23.
    Ritger PL, Peppas NA. A simple equation for the description of solute release, II: Fickian and anomalous release from swellable devices.J Control Release. 1987;5:37–42.CrossRefGoogle Scholar
  24. 24.
    Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers.AAPS PharmSciTech [serial online]. 2006;7:E1.Google Scholar
  25. 25.
    Al-Taani BM, Tashtoush BM. Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium.AAPS PharmSciTech [serial online]. 2003;4:E43.Google Scholar
  26. 26.
    Costa P, Lobo JMS. Modeling and comparison of dissolution profiles.Eur J Pharm Sci. 2001;13:123–133.PubMedCrossRefGoogle Scholar
  27. 27.
    Ford JL, Rubinstein MH, Hogan JE. Formulation of sustained release promethazine hydrochloride tablets using hydroxypropyl methylcellulose matrices.Int J Pharm. 1985;24:327–338.CrossRefGoogle Scholar
  28. 28.
    Ford JL, Rubinstein MH, Hogan JE. Propranolol hydrochloride and aminophylline release from matrix tablets containing hydroxypropyl methylcellulose.Int J Pharm. 1985;24:339–350.CrossRefGoogle Scholar
  29. 29.
    Ford JL, Rubinstein MH, Hogan JE. Dissolution of a poorly water soluble drug, indomethacin, from hydroxypropyl methylcellulose controlled release tablets.J Pharm Pharmacol. 1985;37:33P.Google Scholar
  30. 30.
    Shah N, Zhang G, Apelian V, Zeng F, Infeld MH, Malick AW. Prediction of drug release from hydroxypropyl methylcellulose (HPMC) matrices: effect of polymer concentration.Pharm Res. 1993;10:1693–1695.PubMedCrossRefGoogle Scholar
  31. 31.
    Kim H, Fassihi R. Application of binary polymer system in drug release rate modulation, 2: influence of formulation variables and hydrodynamic conditions on release kinetics.J Pharm Sci. 1997;86:323–328.PubMedCrossRefGoogle Scholar
  32. 32.
    Dahl TC, Calderwood T, Bormeth A, Trimble K, Piepmeir E. Influence of physico-chemical properties of hydroxypropyl methylcellulose in naproxen release from sustained release matrix tablets.J Control Release. 1990;14:1–10.CrossRefGoogle Scholar
  33. 33.
    Liu CH, Kao Y, Chen S, Sokoloski TD, Sheu MT. In-vitro and in-vivo studies of the diclofenac sodium controlled release matrix tablets.J Pharm Pharmacol. 1995;47:360–364.PubMedGoogle Scholar
  34. 34.
    Hiremath SP, Saha RN. Design and study of rifampicin oral controlled release formulations.Drug Deliv. 2004;11:311–317.PubMedCrossRefGoogle Scholar
  35. 35.
    York P. A consideration of experimental variables in the analysis of powder compaction behavior.J Pharm Pharmacol. 1979;31:244–246.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Punna Rao Ravi
    • 1
  • Sindhura Ganga
    • 1
  • Ranendra Narayan Saha
    • 1
  1. 1.Pharmacy Group, Faculty Division IIIBirla Institute of Technology and SciencePilani, RajasthanIndia

Personalised recommendations