ECTS: 15
Hovedvejleder
René Holm, SDU (FKF), reho@sdu.dk, 65502375
Medvejleder
Nadina Zulbeari, SDU (FKF) nazu@sdu.dk, 65507597
Mathias Dam Mønster Sørensen (FKF) mathiasdms@sdu.dk, 65509333
Baggrund for projektet
Long-acting injectables are widely used in the treatment of numerous diseases requiring long-term treatment. These formulations are often prepared as micro- or nanosuspensions achieved through techniques such as wet bead milling, which reduces drug particle sizes to the micron or sub-micron range. However, this reduction in drug particle size increases the surface area, rendering the system thermodynamically unstable. To counteract the rise in Gibbs free energy, the system may minimize the high Gibbs free energy by particle growth mechanisms such as Ostwald ripening and aggregation, which are regarded as stability challenges.
To counteract these issues, selecting appropriate stabilizers (such as surfactants and/or polymers) at optimal concentrations is crucial. This is done through screening studies, which involve a trial-and-error approach where different stabilizers and concentrations are tested to determine which formulations show the smallest change in particle size during storage. Traditionally, the screenings are carried out at a fixed API concentration and storage temperature (e.g. 100 mg/mL API at 40°C). However, it remains unclear whether these conditions are optimal.
This project therefore investigates the influence of different API and surfactant concentrations in suspensions under different temperature conditions to identify the most optimal screening parameters. One focus will be whether surfactant concentration scales linearly with the API concentration (e.g. whether 2% PS20 at 100 mg/mL API corresponds to 6% PS20 at 300 mg/mL API).
Problemformulering
Are classical screening conditions optimal?
Metoder
The manufacturing of the nano- or microsuspensions is prepared by media milling with a dual centrifuge. The stability of the manufactured suspensions is determined through stress stability studies where the particle size distribution is measured over time using laser diffraction.
All data are collected and organized and handed over to the supervisor at the end of the project.
Vejledning
Meetings on a biweekly basis, where the student presents data, interpretations and the next steps to initiate the discussion. Day-to-day interactions are also possible.