**5. Conclusions**

The role of key SLH characteristics on in vitro performance of FEN-loaded SLHs and super-SLH were investigated and compared. It was evident that the silica's internal nanostructure influences lipase accessibility, which, in turn, affects the mechanism of drug release and FEN precipitation behavior. The crystalline FEN present at higher drug loads correlated with poor in vitro performance. Furthermore, the type of lipid utilized to dissolve the drug can impact its encapsulation within silica microparticles and the extent of digestion. When supersaturated, all FS formulations significantly enhanced FEN in vitro dissolution and aqueous solubilization compared to corresponding MPS formulations, crystalline FEN, and APO-fenofibrate. The implications of the main findings suggest that balance between high drug load and performance is key. Therefore, we can conclude that the optimum FEN loading is between 7–16% *w*/*w*, which corresponds to 200–400% Seq. GI lipolysis served as an important test to investigate FEN precipitation in vitro; therefore, future studies with absorption capabilities will be of great benefit to improve the understanding of this trend. Furthermore, the use of C300, a medium chain triglyceride, has proven to be beneficial in enhancing the aqueous solubilization of FEN and demonstrated synergistic action with MPS displaying best aqueous solubilization at 80% Seq, under digesting conditions. This was attributed to C300's ability to generate a larger amount of digestion species along with the slow release kinetics from the restricted pores of MPS, resulting in enhanced FEN solubilization and less precipitation. However, further in vivo investigations are required to validate its full potential. The findings of this research demonstrate the impact of SLH structure and composition in fabricating optimized solid-state LBFs for the oral delivery of PWSDs; since the various silica and lipid types provide competitive advantages, formulations can be tailored depending on the release profile or outcome desired.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/7/687/s1, Table S1: Drug loading efficiencies of 3 FEN-loaded formulations (values represent mean ± SD, *n* = 3), Table S2: The lipid content of the formulations and lipid dosed to lipolysis vessel. Figure S1. The relationship between XRPD peak intensity at 22.3◦ (2θ) and supersaturated drug loading (Seq) for FS PG8 formulations and MPS PG8 formulations, Figure S2. The % phase partitioning of FEN between the aqueous phase and pellet over 90 min after a 3 mg FEN dose of 80% formulations, Crystalline FEN and APO-fenofibrate, under biorelevant gastric and intestinal conditions. Values represent mean ± SD, *n* = 3 and Figure S3. The % phase partitioning of FEN between the aqueous phase and pellet over 90 min after a 3 mg FEN dose of supersaturated formulations, under biorelevant gastric and intestinal conditions. Values represent mean ± SD, *n* = 3.

**Author Contributions:** Conceptualization, R.A., H.B.S. and C.A.P.; Formal analysis, R.A. and P.J.; Funding acquisition, C.A.P.; Investigation, R.A.; Methodology, R.A. and P.J.; Supervision, N.T., K.E.B. and C.A.P.; Validation, R.A.; Writing—original draft, R.A.; Writing—review & editing, P.J., H.B.S., N.T., K.E.B. and C.A.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Australian Research Council Centre of Excellence in Bio-Nano Science and Technology, grant number ARC CE140100036.

**Acknowledgments:** The Australian Government Research Training Program is acknowledged for the master's Scholarship of Ruba Almasri.

**Conflicts of Interest:** The authors declare no conflict of interest.
