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

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)

Abstract

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)

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.