Hydrogenated phospholipid, a promising excipient in amorphous solid dispersions of fenofibrate for oral delivery: Preparation and in-vitro biopharmaceutical characterization.

Amorphous solid dispersions (ASD) represent a viable formulation strategy to improve dissolution and bioavailability of poorly soluble drugs. Our study aimed to evaluate the feasibility and potential role of hydrogenated phospholipid (HPL) as a matrix material and solubilizing additive for binary (alone) or ternary (in combination with polymers) solid dispersions, using fenofibrate (FEN) as the model drug. FEN, incorporated within ASDs by melting or freeze-drying (up to 20% m/m), stayed amorphous during short-term stability studies. The solubility enhancing potential of HPL depended on the dissolution medium. In terms of enhancing in vitro permeation, solid dispersions with HPL were found equally or slightly more potent as compared to the polymer-based ASD. For studied ASD, in vitro permeation was found substantially enhanced as compared to a suspension of crystalline FEN and at least equal compared to marketed formulations under comparable conditions (literature data). Additionally, while the permeation of neat FEN and FEN in binary solid dispersions was affected by the dissolution medium (i.e., the "prandial state"), for ternary solid dispersions the permeation was independent of the "prandial state" (FaSSIF = FeSSIF). This suggests that ternary solid dispersions containing both polymer and HPL may represent a viable formulation strategy to mitigate fenofibrate's food effect.

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Paulina Skupin-Mrugalska reports financial support was provided by Phospholipid Research Center. Mikolaj Czajkowski reports financial support was provided by Phospholipid Research Center. Martin Brandl reports a relationship with Phospholipid Research Center that includes: funding grants. Ann-Christin Jacobsen reports a relationship with Phospholipid Research Center that includes: funding grants. Paulina Skupin-Mrugalska reports a relationship with APV Mainz that includes: travel reimbursement. Martin Brandl reports a relationship with APV Mainz that includes: travel reimbursement. Ann-Christin Jacobsen reports a relationship with APV Mainz that includes: travel reimbursement. Annette Bauer-Brandl reports a relationship with APV Mainz that includes: travel reimbursement. Martin Brandl reports a relationship with University of Maryland Baltimore that includes: travel reimbursement. Annette Bauer-Brandl reports a relationship with University of Maryland Baltimore that includes: travel reimbursement. Annette Bauer-Brandl has patent PermeaPad patent owned by SDU licensed to out-licensed to InnoMe.].