The influence on the oral bioavailability of solubilized and suspended drug in a lipid nanoparticle formulation: In vitro and in vivo evaluation

The present study investigated the oral bioavailability of celecoxib when incorporated into solid lipid nanoparticles either dissolved or suspended. In vitro drug release in different media, in vivo performance, and in vitro-in vivo correlation were conducted. The results revealed that the compound was successfully encapsulated into the nanocarriers with good physicochemical properties for oral administration. The in vitro release profiles followed the Weibull model, with significant differences between the formulations containing the solubilized and the suspended compound. Furthermore, in vitro release data could be used to rank the observed in vivo bioavailability.

Highlights

• The poorly water-soluble drug was successfully entrapped into SLNs for oral delivery.

• In vitro release data was able to predict the rank order of the oral bioavailability.

• The SLN formulations enhanced the bioavailability by 2.5 and 1.8 fold.

• Lipid concentration and particle size had an impact on the bioavailability.

• In vitro-in vivo correlation was achieved using numerical deconvolution.

The relative bioavailability of celecoxib from the solid lipid nanoparticles was 2.5- and 1.8-fold higher for the drug solubilized and suspended solid lipid nanoparticle formulation, respectively, when compared to the celecoxib reference. A significant difference was observed between the plasma concentration–time profiles and pharmacokinetic parameters for the three investigated formulations. Finally, this investigation displayed promising outcomes that both solubilized and suspended celecoxib in the lipid core of the solid lipid nanoparticles offers the potential to improve the compound’s oral bioavailability and thereby reduce the dosing frequency.

Read more

Kimberley Elbrink, Sofie Van Hees, Dirk Roelant, Tine Loomans, René Holm, Filip Kiekens, The influence on the oral bioavailability of solubilized and suspended drug in a lipid nanoparticle formulation: In vitro and in vivo evaluation, European Journal of Pharmaceutics and Biopharmaceutics, Volume 179, 2022, Pages 1-10, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2022.08.010