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Design and study of lamivudine oral controlled release tablets

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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.

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References

  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. 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. 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.

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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. Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity.Clin Ther. 2000;22:911–936.

    Article  PubMed  CAS  Google Scholar 

  9. Vargas CI, Ghaly ES. Kinetic release of theophylline from hydrophilic swellable matrices.Drug Dev Ind Pharm. 1999;25:1045–1050.

    Article  PubMed  CAS  Google Scholar 

  10. Ranga RKV, Padmalatha DK, Buri B. Cellulose matrices for zero-order release of soluble drugs.Drug Dev Ind Pharm. 1988;14:2299–2320.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  19. Narasimhan B, Peppas NA. Disentanglement and repetition during dissolution of rubbery polymers.J Polym Sci Part B: Polym Phys. 1996;34:947–961.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  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.

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

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  34. Hiremath SP, Saha RN. Design and study of rifampicin oral controlled release formulations.Drug Deliv. 2004;11:311–317.

    Article  PubMed  CAS  Google Scholar 

  35. York P. A consideration of experimental variables in the analysis of powder compaction behavior.J Pharm Pharmacol. 1979;31:244–246.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pharmacy Group, Faculty Division III, Birla Institute of Technology and Science, 333 031, Pilani, Rajasthan, India

    Punna Rao Ravi, Sindhura Ganga & Ranendra Narayan Saha

Authors
  1. Punna Rao Ravi
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  2. Sindhura Ganga
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  3. Ranendra Narayan Saha
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Corresponding author

Correspondence to Ranendra Narayan Saha.

Additional information

Themed Issue: Oral Controlled Release Development and Technology

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

Published: December 7, 2007

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Ravi, P.R., Ganga, S. & Saha, R.N. Design and study of lamivudine oral controlled release tablets. AAPS PharmSciTech 8, 101 (2007). https://doi.org/10.1208/pt0804101

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  • DOI: https://doi.org/10.1208/pt0804101

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