ECTS: 15
Hovedvejleder: René Holm, 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
Wet bead media milling is a well-known size reduction approach used for the preparation of pharmaceutical suspensions intended for long-acting injectables (LAIs). During milling, poorly water-soluble, crystalline drug particles are suspended in an aqueous stabilizer medium containing milling beads that reduce the sizes of drug particles as a result of particle-bead collisions. The milling efficiency is, however, impacted by multiple parameters as for instance the drug compounds grindability, bead type and size, milling intensity, and milling time. The most common bead type for media milling is yttrium-stabilized zirconium oxide milling beads as they hold a high crushing strength with high stability (i.e., wear-resistance), suitable for pharmaceutical applications while they can be obtained in various sizes. Theoretically, smaller milling beads tend to result in smaller sizes of drug particles due to the increased contact points at a larger surface area, increasing the milling intensity which is necessary for some drug compounds with restricted grindability. On the contrary, some compounds can be sensitive to too high milling intensity, as it can result in crystal defects. Mixtures of large and small zirconium beads could potentially oppose this while still allowing an improved milling efficiency due to increased contact points from various bead sizes without compromising the compound characteristics.
The project will therefore work with two different model compounds, haloperidol and indomethacin, as plastic compound and surface-sensitive compound, respectively, to examine if a higher grinding capacity is achieved when bead mixtures containing different sizes of zirconium beads can be achieved for suspensions prepared by the dual centrifugation approach. Different combinations of bead size mixtures will therefore be examined.
Problemformulering
Is it possible to improve the milling efficiency of non-brittle compounds as well as surface-sensitive compounds using bead mixtures containing zirconium beads in different sizes?
Metoder
Suspensions will be prepared using media milling by dual centrifugation and characterized by laser diffraction.
All data generated are physical-chemical in nature, hence not associated with any special ethical concerns. All raw data are collected and organized in an easy-to-understand way – and handed over to the supervisor at the end of the project.
Vejledning
Biweekly meetings that include data presentation and interpretations for discussions. Daily interactions are also available for guidance.