Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions

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• 作者：Matthias Manne Knopp^a ; ^b ; Julia Hoang Nguyen^a ; ^c ; Christian Becker^b ; Nadine Monika Francke^b ; Erling B. Jø ; rgensen^a ; Per Holm^a ; René ; Holm^a ; ^c ; ^{rhol@lundbeck.com" class="auth_mail" title="E-mail the corresponding author} ; Huiling Mu^c ; Thomas Rades^c ; Peter Langguth^b
• 关键词：PVP ; Molecular weight ; Amorphous solid dispersion ; ​In vitro ; Non-sink dissolution ; Celecoxib ; In vivo ; IVIVC
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：145-151
• 全文大小：377 K

文摘

In this study, the influence of the molecular weight of polyvinylpyrrolidone (PVP) on the non-sink in vitro dissolution and in vivo performance of celecoxib (CCX):PVP amorphous solid dispersions were investigated. The dissolution rate of CCX from the amorphous solid dispersions increased with decreasing PVP molecular weight and crystallization inhibition was increased with increasing molecular weight of PVP, but reached a maximum for PVP K30. This suggested that the crystallization inhibition was not proportional with molecular weight of the polymer, but rather there was an optimal molecular weight where the crystallization inhibition was strongest.

Consistent with the findings from the non-sink in vitro dissolution tests, the amorphous solid dispersions with the highest molecular weight PVPs (K30 and K60) resulted in significantly higher in vivo bioavailability (AUC_0–24h) compared with pure amorphous and crystalline CCX.

A linear relationship between the in vitro and in vivo parameter AUC_0–24h indicated that the simple non-sink in vitro dissolution method used in this study could be used to predict the in vivo performance of amorphous solid dispersion with good precision, which enabled a ranking between the different formulations. In conclusion, the findings of this study demonstrated that the in vitro and in vivo performance of CCX:PVP amorphous solid dispersions were significantly controlled by the molecular weight of the polymer.