Phospholipids as excipients in Amorphous Solid Dispersions – an attempt to establish hot-melt-extrusion for oral formulations of poorly soluble drugs

People involved

Professor Dr. Martin Brandl (collaborator) – Drug Transport and Delivery Group, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense DK-5230, Denmark (mmb@sdu.dk)

Dr. Edyta Szalek (collaborator) – Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences (eszalek@ump.edu.pl)

Dr. Agnieszka Karbownik (collabortor) – Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences (agnieszkakarbownik@o2.pl)

Kinga Biedrzycka, M.Sc.Eng. (collaborator) – Applied Manufacturing Science (kinga.biedrzycka@ams-pharma.org)

Abstract

The aim of the project is the usage of phospholipids as components of mixed phospholipid and polymer-based amorphous solid dispersions for oral delivery of poorly soluble drugs. Selected formulations will be screened by using derivatives of cellulose or polyvinylpyrrolidone and (hydrogenated) phospholipids. Initially, Fenofibrate (FEN), an orally active lipid-regulating drug, will be used as a model drug in the project. FEN is a Biopharmaceutical Classification System (BCS) class II drug in which its oral bioavailability is limited by poor aqueous solubility. Amorphous solid dispersions of drug substance in a polymer-phospholipid matrix will initially be prepared by simple film-casting/batch-melting and later by hot-melt extrusion. FEN is commonly used as a model drug for amorphous solid dispersion studies and has been reported as a suitable candidate for hot-melt extrusion manufacturing.1,2) The effect of phospholipid on the formation of amorphous solid dispersion of FEN will be evaluated by screening techniques, including analysis of dispersed mixed films. Further, the pharmaceutical performance of formulations will be studied by dissolution testing in biorelevant media. Special efforts will be focused on establishing a hot-melt extrusion process for the preparation of FEN amorphous solid dispersion in a polymer/phospholipid matrix. Finally, the bioavailability of a drug in selected formulations with and without phospholipids will be compared with an originator  in vivo.

Benefit for the community

The innovative aspect of the project embraces carriers for oral application, based on mixed, matrices composed of polymers and (hydrogenated) phospholipids, in which drug is present in an amorphous state. These carriers presumably may increase the bioavailability of the incorporated drug and have not been so far screened and characterized in detail. Therefore, it is assumed that the research project outcome will increase the interest in the application of hydrogenated phospholipids as an excipient for oral formulations.

Visit the supervisors lab

Poznan University of Medical Sciences and Dr Paulina Skupin-Mrugalska