Candesartan cilexetil in vitro–in vivo correlation: Predictive dissolution as a development tool

Andrés Figueroa-Campos, Bárbara Sánchez-Dengra, Virginia Merino, Arik Dahan, Isabel González-Álvarez, Alfredo García-Arieta, Marta González-Álvarez, Marival Bermejo

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The main objective of this investigation was to develop an in vitro–in vivo correlation (IVIVC) for immediate release candesartan cilexetil formulations by designing an in vitro dissolution test to be used as development tool. The IVIVC could be used to reduce failures in future bioequivalence studies. Data from two bioequivalence studies were scaled and combined to obtain the dataset for the IVIVC. Two-step and one-step approaches were used to develop the IVIVC. Experimental solubility and permeability data confirmed candesartan cilexetil. Biopharmaceutic Classification System (BCS) class II candesartan average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed. Fractions dissolved were obtained in several conditions in USP II and IV apparatus and the results were compared calculating the f2 similarity factor. Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the products of candesartan cilexetil employed the USP IV apparatus and a three-step pH buffer change, from 1.2 to 4.5 and 6.8, with 0.2% of Tween 20. This new model was able to predict the in vivo differences in dissolution and it could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Original languageEnglish
Article number633
Pages (from-to)1-21
Number of pages21
JournalPharmaceutics
Volume12
Issue number7
DOIs
StatePublished - 1 Jul 2020

Keywords

  • BCS
  • Bioequivalence
  • Candesartan cilexetil
  • IVIVC
  • Predictive in vivo-dissolution

ASJC Scopus subject areas

  • Pharmaceutical Science

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