Insight into the mechanism behind oral bioavailability-enhancement by nanosuspensions through combined dissolution/permeation studies
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https://hdl.handle.net/10037/28738Date
2023-03-02Type
Journal articleTidsskriftartikkel
Peer reviewed
Author
Lynnerup, Jakob Tobias; Eriksen, Jonas Borregaard; Bauer-Brandl, Annette; Holsæter, Ann Mari; Brandl, MartinAbstract
As numerous new drug candidates are poorly water soluble, enabling formulations are needed to increase their
bioavailability for oral administration. Nanoparticles are a conceptually simple, yet resource consuming strategy
for increasing drug dissolution rate, as predicting in vivo oral absorption using in vitro dissolution remains
difficult. The objective of this study was to obtain insight into nanoparticle characteristics and performance
utilizing an in vitro combined dissolution/permeation setup. Two examples of poorly soluble drugs were
examined (cinnarizine and fenofibrate). Nanosuspensions were produced by top-down wet bead milling using
dual asymmetric centrifugation, obtaining particle diameters of approx. 300 nm. DSC and XRPD studies indicated
that nanocrystals of both drugs were present with retained crystallinity, however with some disturbances.
Equilibrium solubility studies showed no significant increase in drug solubility over the nanoparticles, as
compared to the raw APIs. Combined dissolution/permeation experiments revealed significantly increased
dissolution rates for both compounds compared to the raw APIs. However, there were substantial differences
between the dissolution curves of the nanoparticles as fenofibrate exhibited supersaturation followed by precipitation, whereas cinnarizine did not exhibit any supersaturation, but instead a shift towards faster dissolution
rate. Permeation rates were found significantly increased for both nanosuspensions when compared to the raw
APIs, indicating a direct implication that formulation strategies are needed, be it stabilization of supersaturation
by precipitation inhibition and/or dissolution rate enhancement. This study indicates that in vitro dissolution/
permeation studies can be employed to better understand the oral absorption enhancement of nanocrystal
formulations.
Publisher
ElsevierCitation
Lynnerup, Eriksen, Bauer-Brandl, Holsæter, Brandl. Insight into the mechanism behind oral bioavailability-enhancement by nanosuspensions through combined dissolution/permeation studies. European Journal of Pharmaceutical Sciences. 2023Metadata
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