Predicting in vivo performance of fenofibrate amorphous solid dispersions using in vitro non-sink dissolution and dissolution permeation setup

Research output: Contribution to journalJournal articleResearchpeer-review

  • Karoline Aagaard Lentz
  • Jakob Plum
  • Bente Steffansen
  • Per Ola Arvidsson
  • Diana Højmark Omkvist
  • Anders Just Pedersen
  • Carl Johan Sennbro
  • Gitte Pommergaard Pedersen
  • Jacobsen, Jette

Amorphous solid dispersion (ASD) is emerging as a useful formulation strategy to increase the bioavailability of active pharmaceutical ingredients with poor solubility. In vitro dissolution testing under non-sink conditions has often been used to evaluate the ability of ASDs to generate and maintain supersaturation to predict the in vivo performance. However, such a single compartment dissolution setup can fail to predict the oral bioavailability, due to an interdependence between precipitation and permeation. Hence, the use of two compartment dissolution-permeation setups is emerging. In this study, three ASDs containing fenofibrate as model drug substance were developed using Soluplus®, and Hypromellose Acetate Succinate in two different grades (high and low), respectively. The aim was to compare the use of a small-scale in vitro non-sink dissolution setup and a small-scale in vitro dissolution-permeation setup to predict the in vivo oral exposure of the ASDs in rats. The maximum concentration (Cmax) and area under curve (AUC) obtained in the in vitro studies were used to predict the in vivo rank order of the formulations. The results showed that the two in vitro studies resulted in the same rank order based on both Cmax and AUC. Interestingly, Cmax resulted in a better in vitro/in vivo correlation than the in vitro AUC, and based on the in vitro Cmax, the in vivo rank order was predicted.

Original languageEnglish
Article number121174
JournalInternational Journal of Pharmaceutics
Volume610
Number of pages8
ISSN0378-5173
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier B.V.

    Research areas

  • Amorphous solid dispersion, Dissolution/permeation, Fenofibrate, Formulation development, Oral rat pharmacokinetics, Predictive dissolution

ID: 283782539