Surface responses and desirability functions to determine optimal granulation domains

Drug Dev Ind Pharm. 2010 Sep;36(9):1016-26. doi: 10.3109/03639041003598978.

Abstract

Background: Single pot mixer-granulator-dryer (high-shear granulator with in situ double jacket vacuum drying) and multiphase equipment (high-shear granulator associated with fluid bed dryer) are classically used for wet granulation. At present time, industrial production imperatives may require to switch one formulation from one equipment to another.

Method: To compare the two processes and to define, for each of them, the optimal formulation domain, experiments were organized according to Doehlert experimental designs. Response surfaces were used to identify the levels of each factor (binder and filler ratios) inducing the more satisfying responses. The contribution of binder and filler ratios to granule properties was highlighted according to the process. Then the desirability function was used to determine and compare the optimal formulation domain for each process.

Results and conclusion: In the studied formulation domain and for the considered equipment, the transposition from a single pot to a multiphase high-shear granulation process did not seem to raise difficulties; the same formulations were out of specification for both processes and other trials, the technological properties were maintained or improved in the Fielder/Niro equipment.

MeSH terms

  • Desiccation
  • Dosage Forms
  • Drug Compounding* / instrumentation
  • Drug Compounding* / methods
  • Excipients*
  • Particle Size
  • Pharmaceutical Preparations / chemistry*
  • Porosity
  • Solubility
  • Surface Properties
  • Tablets
  • Technology, Pharmaceutical*

Substances

  • Dosage Forms
  • Excipients
  • Pharmaceutical Preparations
  • Tablets