Box-behnken design for the optimization of formulation variables of indomethacin coprecipitates with polymer mixtures Academic Article uri icon


  • Numerous reports explain the dissolution release mechanisms and certain matrix type formulations follow the Higuchi's square root of time model. Earlier screening experiments have shown that compression of indomethacin coprecipitates prepared using Eudragit polymer mixtures yielded matrix tablets which release 80% of the drug in 24 h. The present study deals with optimization of formulation variables to improve dissolution characteristics of the matrix formulation. A three-factor, three-level Box-Behnken design with drug to polymer ratio (X1), polymer to polymer ratio (X2) and solvent ratio (X3) as the independent variables were selected for the study. The dependent variable was cumulative percent of drug released in 24 h. As a novel approach, constraints were placed on the dependent variable such that the ideal release characteristics of a matrix formulation would be obtained for the 24-h release formulation. Based on the experimental design, different indomethacin release rates and profiles were obtained. The dependent and independent variables were related using mathematical relationships and surface response plots. The model predicted a 100.7% release with the X1, X2 and X3 levels of 7.813, 0.9586 and 1.5, respectively. The optimized formulation prepared according to predicted levels provided release rates which were close to predicted values. Also, the observed and predicted response values fell in the range of calculated values as obtained from the Higuchi's model. Further, the optimized formulation was compared with solid dispersions and physical mixtures. All the formulations were characterized by X-ray diffraction, IR DSC and dissolution studies.

published proceedings

  • International Journal of Pharmaceutics

altmetric score

  • 0.25

citation count

  • 51

complete list of authors

  • Karnachi, A

publication date

  • April 1996