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Article / 2017

In vitro - in vivo Correlations of Carbamazepine Nanodispersions for Application in Formulation Development

  • Michael Puppolo
  • Zachary Warnken
  • Iris Duarte
  • Traciann Dillon
  • David Storey
Journal of pharmaceutical sciences, ISSN: 1520-6017, Vol: 107, Issue: 1, Page: 453-465
During formulation development, efficiently integrating in vitro dissolution testing can significantly improve one's ability to estimate in vivo performance and aide in the selection of premier drug candidates. The concept of in vitro–in vivo relationship/correlation has garnered significant attention from pharmaceutical scientists to predict expected bioavailability characteristics for drug substances and products. The present work illustrates a comparative evaluation of in vitro tests to access crystalline carbamazepine and various types of amorphous and crystalline dispersions of carbamazepine and Eudragit® L100 produced by spray drying, including a membrane-permeation dissolution methodology and nonsink dissolution. To establish the best model, parameters such as pH, membrane constitution, and dissolution media composition were investigated. The in vitro results were compared against in vivomice pharmacokinetic studies and qualitatively, the membrane-permeation dissolution methodology correlated well with in vivo. Various correlations were performed in order to evaluate the optimal model for characterizing the relationship. Results exhibited a coefficient of determination (R2) values of 0.90 and 1.00, depicting a linear relationship of the data in comparison. Therefore, for the current formulation system (drug/polymer/technique), membrane-permeation dissolution can guide formulation development and potentially reduce the number of animal and clinical pharmacokinetic studies required.