In vivo performance of amorphous solid dispersions based on water-insoluble versus water-soluble carriers:...

The objective of this study is to address the unanswered question whether sustained supersaturation generated from amorphous solid dispersions (ASDs) formulated in insoluble hydrogel carriers will result in better bioavailability over that of spring-and-parachute type of dissolution profiles of ASDs formulated in water-soluble carriers. This was achieved by investigating the effects of supersaturation generation rates and doses on the extent of absorption (i.e., AUC) of Fenofibrate (FNB), a poorly-soluble model drug, from ASDs based on crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA), physically crosslinked poly(vinyl alcohol) (PVA), and polyvinylpyrrolidone (PVP) in a rat model. Absorption modeling was conducted using GastroPlus® 9.7 to evaluate in vivo dissolution and absorption characteristics of FNB from these ASDs. The results show that the extent of FNB absorption from the rapid dissolution-controlled supersaturation build-up of PVP ASD was comparable to that of the gradual diffusion-controlled supersaturation generation from more hydrophilic PVA ASD; but both were higher than that of the less hydrophilic PHEMA ASD. The results also show that a moderate decrease in supersaturation rate is beneficial to the absorption of FNB. Moreover, this study confirms it is indeed possible to obtain similar exposure with lower doses of FNB when ASD formulations are employed as strategies for bioavailability enhancement.