Rational estimation of the optimum amount of non-fibrous disintegrant applying percolation theory for binary fast disintegrating formulation

J Pharm Sci. 2008 Jan;97(1):529-41. doi: 10.1002/jps.21163.


The purpose of this study was to propose a method of determining the exact value of disintegrant ratio in a binary drug-disintegrant compacted mixture for a minimum disintegration time in the case of spherical particles. Disintegration is a limiting factor in dissolution process of compact for low water soluble active ingredients. As disintegration time is shortest at a certain ratio of disintegrant, a calculation of this value is important for solid dosage from design to enhance disintegration and dissolution process. According to percolation theory, a minimum disintegration time corresponds to the formation of a continuous water-conducting cluster through the entire tablet. The critical volumetric ratio at which the cluster is formed is named percolation threshold and has the value of 0.16 for random close packed (RCP) sphere systems. RCP systems where chosen as the best model for compacts consisting of spherical particles. Two cases for water diffusion through the tablet were identified, according to geometrical considerations between disintegrant and drug particles. These cases determine if disintegrant particles can have a contact between each other within the compact and thus if porosity and disintegrant volume are included in the continuous cluster. An equation for both cases is presented in the form of piecewise function to determine the minimal disintegrant volumetric ratio for a binary drug/disintegrant compact in order to achieve a minimum disintegration time. Disintegration tests were performed with tablets at different ratios of modified corn starch mixed with caffeine or paracetamol powders. Estimated and experimental optimal ratio were compared showing coefficient R(2) = 0.96.

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / chemistry
  • Algorithms
  • Caffeine / administration & dosage
  • Caffeine / chemistry
  • Chemical Phenomena
  • Chemistry, Pharmaceutical / statistics & numerical data*
  • Chemistry, Physical
  • Diffusion
  • Drug Compounding
  • Excipients / chemistry*
  • Models, Statistical
  • Particle Size
  • Porosity
  • Powders
  • Tablets
  • Water / chemistry


  • Excipients
  • Powders
  • Tablets
  • Water
  • Acetaminophen
  • Caffeine