Formulation development and evaluation of lamivudine controlled release tablets using cross-linked sago starch

Expert Opin Drug Deliv. 2013 Feb;10(2):173-82. doi: 10.1517/17425247.2013.738665. Epub 2012 Dec 14.

Abstract

Objectives: Modified starches based polymeric substances find utmost applicability in pharmaceutical formulation development. Cross-linked starches showed very promising results in drug delivery application. The present investigation concerns with the development of controlled release tablets of lamivudine using cross-linked sago starch.

Methods: The cross-linked derivative was synthesized with phosphorous oxychloride and native sago starch in basic pH medium. The cross-linked sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulated tablets were evaluated for various physical characteristics, in vitro dissolution release study and in vivo pharmacokinetic study in rabbit model.

Results: In vitro release study showed that the optimized formulation exhibited highest correlation (R) in case of zero order kinetic model and the release mechanism followed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2), and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®.

Conclusion: The cross-linked starch showed promising results in terms of controlling the release behavior of the active drug from the matrix. The hydrophilic matrix synthesized by cross-linking could be used with a variety of active pharmaceutical ingredients for making their controlled/sustained release formulations.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacokinetics
  • Area Under Curve
  • Arecaceae
  • Chemistry, Pharmaceutical*
  • Delayed-Action Preparations
  • Drug Compounding*
  • Drug Delivery Systems
  • Excipients / chemistry
  • Lamivudine / chemistry*
  • Lamivudine / pharmacokinetics
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Starch / chemistry*
  • Tablets*

Substances

  • Anti-HIV Agents
  • Delayed-Action Preparations
  • Excipients
  • Tablets
  • Lamivudine
  • Starch