In depth mechanistic biopharmaceutical investigation of oral phospholipid-based formulations for poorly soluble drugs

Prof. Dr. Martin Brandl1) and Dr. Ann-Christin Jacobsen1) – University of Southern Denmark, Odense/Denmark

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Professor Dr. Martin Brandl and Dr. Ann-Christin JacobsenUniversity of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Campusvej 55, 5230 Odense M, Denmark

People involved

Dr. Ann-Christin Jacobsen  (Postdoc sponsored by the PRC) - University of Southern Denmark, Odense/Denmark

Dr. Paulina Skupin-Mruglaska (collaborator) - Poznan University of Medical Sciences (see PRC project of Dr. Skupin-Mrugalska)


The biopharmaceutical behavior of phospholipid-based enabling formulations of poorly soluble drugs is complex due to the gastrointestinal processing of phospholipids (e.g., enzymatic breakdown)1) and the formation of nano-sized structures (e.g., liposomes and mixed micelles)2). Typically, enabling formulations also induce supersaturation, which further increases complexity.

Experimental evidence indicates that drug solubilized by nano-sized structures and molecularly dissolved drug contribute to oral absorption in different ways: The molecularly dissolved drug determines rate and extent of oral absorption and nano-sized structures may act as a reservoir. Traditional biopharmaceutical tools cannot resolve the distribution of the drug between the molecularly dissolved state and drug associated with nano-sized structures nor the related kinetics.

In this project, a biopharmaceutical approach that can resolve how the drug is distributed between different phases and which nano-sized structures evolve during gastrointestinal processing of phospholipid-based enabling formulations will be established (Figure 1)

Figure 1. Schematic overview of the proposed biopharmaceutical characterization approach to obtain an in-depth mechanistic understanding of the performance of phospholipid-based oral formulations.

The approach is based on in vitro lipolysis to mimic the gastrointestinal processing1)3) in combination with two innovative tools: (1) microdialysis sampling to determine the molecularly dissolved drug4) and (2) field flow fractionation (AF4/MALLS)2) to resolve the ultrastructural pattern of co-existing colloidal states during lipolysis.

Benefit for the community

A biopharmaceutical approach will be established that combines in vitro lipolysis, microdialysis sampling and AF4-MALLS. This combination is expected to help formulation experts to gain an in-depth mechanistic understanding of the behavior of phospholipid-based enabling formulations in the gastrointestinal tract. Thereby, hopefully, future development of phospholipid-based enabling formulations can be facilitated.

Visit the supervisors lab

Contact to Drug Transport & Delivery at the University of Southern Denmark.

Prof. Martin Brandl and Dr. Ann-Christin Jacobsen.

Parmentier J, Thomas N, Muellertz A, Fricker G, Rades T, 2012
Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis
Int. J. Pharm. 437, 253-263
Elvang PA, Jacobsen AC, Bauer-Brandl A, Stein PC, Brandl M, 2018
Co-existing colloidal phases in artificial intestinal fluids assessed by AF4/MALLS and DLS: A systematic study into cholate & (lyso-) phospholipid blends, incorporating celecoxib as a model drug
Eur. J. Pharm. Sci. 120, 61-72
Jacobsen AC, Kabedev A, Sinko PD, Palm JE, Bergström CAS, Teleki A, 2022
Intrinsic lipolysis rate for systematic design of lipid-based formulations
Drug Delivery Transl. Res.
Holzem FL, Schaffland JP, Brandl M, Bauer-Brandl A, Stillhart C, 2022
Microdialysis and nanofiltration allow to distinguish molecularly dissolved from colloid-associated drug concentrations during biomimetic dissolution testing of supersaturating formulations
Eur. J. Pharm. Sci. 174, 106166
Publications derived from the project:
Czajkowski M, Jacobsen AC, Bauer-Brandl A, Brandl M, Skupin-Mrugalska P, 2023
Hydrogenated phospholipid, a promising excipient in amorphous solid dispersions of fenofibrate for oral delivery: Preparation and in-vitro biopharmaceutical characterization
Int. J. Pharm. 644, 123294
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