TY - JOUR
T1 - Candesartan cilexetil in vitro–in vivo correlation
T2 - Predictive dissolution as a development tool
AU - Figueroa-Campos, Andrés
AU - Sánchez-Dengra, Bárbara
AU - Merino, Virginia
AU - Dahan, Arik
AU - González-Álvarez, Isabel
AU - García-Arieta, Alfredo
AU - González-Álvarez, Marta
AU - Bermejo, Marival
N1 - Funding Information: This research was funded by the Agencia Estatal de Investigaci?n and the European Union, through FEDER (Fondo Europeo de Desarrollo Regional), grant number SAF2016-78756 (AEI/FEDER, EU). B?rbara S?nchez-Dengra received a grant from the Ministry of Science, Innovation and Universities of Spain, grant number FPU17/00530. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - BCS
KW - Bioequivalence
KW - Candesartan cilexetil
KW - IVIVC
KW - Predictive in vivo-dissolution
UR - http://www.scopus.com/inward/record.url?scp=85087573363&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12070633
DO - 10.3390/pharmaceutics12070633
M3 - Article
C2 - 32640620
SN - 1999-4923
VL - 12
SP - 1
EP - 21
JO - Pharmaceutics
JF - Pharmaceutics
IS - 7
M1 - 633
ER -