Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier
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Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier. / Wendelboe, Johan; Knopp, Matthias Manne; Khan, Fauzan; Chourak, Nabil; Rades, Thomas; Holm, René.
In: International Journal of Pharmaceutics, Vol. 531, No. 1, 05.10.2017, p. 324-331.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier
AU - Wendelboe, Johan
AU - Knopp, Matthias Manne
AU - Khan, Fauzan
AU - Chourak, Nabil
AU - Rades, Thomas
AU - Holm, René
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - The present study investigated the influence of in vitro dissolution conditions on the in vivo predictability of an amorphous solid dispersion of celecoxib (CCX) in the pH-sensitive polymer Eudragit(®) S 100. Different doses of a 25:75w/w% CCX:Eudragit(®) S 100 amorphous solid dispersion (CCX:EUD) were investigated. During in vitro dissolution a significant effect of the pH of the dissolution media on the release of CCX was observed. In fasted state simulated intestinal fluid (FaSSIF) pH 6.5, the release of CCX from the amorphous solid dispersion was comparable to that of crystalline CCX and lower than that of amorphous CCX whereas in FaSSIF pH 7.4, the release was significantly increased compared to both crystalline and amorphous CCX. With a 3-fold increase in the exposure of CCX:EUD compared to crystaline CCX. The in vivo data also suggested that Eudragit(®) S 100 was suitable as a carrier in amorphous solid dispersions of CCX. In vitro-in vivo correlation demonstrated that the in vitro data obtained in FaSSIF pH 7.4 was more predictive for the in vivo performance than that obtained in FaSSIF pH 6.5. Consequently, the findings of this study underline that when predicting the in vivo performance of amorphous solid dispersions with pH-sensitive polymers, it is imperative that the in vitro dissolution conditions are carefully considered.
AB - The present study investigated the influence of in vitro dissolution conditions on the in vivo predictability of an amorphous solid dispersion of celecoxib (CCX) in the pH-sensitive polymer Eudragit(®) S 100. Different doses of a 25:75w/w% CCX:Eudragit(®) S 100 amorphous solid dispersion (CCX:EUD) were investigated. During in vitro dissolution a significant effect of the pH of the dissolution media on the release of CCX was observed. In fasted state simulated intestinal fluid (FaSSIF) pH 6.5, the release of CCX from the amorphous solid dispersion was comparable to that of crystalline CCX and lower than that of amorphous CCX whereas in FaSSIF pH 7.4, the release was significantly increased compared to both crystalline and amorphous CCX. With a 3-fold increase in the exposure of CCX:EUD compared to crystaline CCX. The in vivo data also suggested that Eudragit(®) S 100 was suitable as a carrier in amorphous solid dispersions of CCX. In vitro-in vivo correlation demonstrated that the in vitro data obtained in FaSSIF pH 7.4 was more predictive for the in vivo performance than that obtained in FaSSIF pH 6.5. Consequently, the findings of this study underline that when predicting the in vivo performance of amorphous solid dispersions with pH-sensitive polymers, it is imperative that the in vitro dissolution conditions are carefully considered.
KW - Journal Article
U2 - 10.1016/j.ijpharm.2017.08.078
DO - 10.1016/j.ijpharm.2017.08.078
M3 - Journal article
C2 - 28827200
VL - 531
SP - 324
EP - 331
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -
ID: 185403952