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
Wet bead media milling is a well-known milling approach to prepare pharmaceutical suspensions. During media milling, drug particles are suspended in an aqueous stabilization medium, where sizes of drug particles are reduced from friction and collisions between the drug particles and milling beads. The milling efficiency can thereby, among others, be directed by the bead type and size, which can be used to adjust the desired particle size profile of the suspension. Hard, spherical, yttrium-stabilized zirconium oxide beads are typically utilized as milling beads for pharmaceutical purposes due to their high crushing strength and high shear-stability. Cross-linked polystyrene beads have also been proposed in the literature to function as efficient milling beads with a lower risk of mechanically induced degradation of shear-sensitive compounds as they are softer and more deformable. Previous findings of partial surface amorphization after milling with dual centrifugation have also been observed for a single drug compound when suspensions were milled with zirconium beads and opposed when milled with polystyrene beads. Unwanted surface amorphization can alter the desired suspension characteristics both in terms of solubility and physical stability which, ultimately, can impact the desired release rate when intended for long-acting injectables.
The project will therefore work with a series of different model compounds to examine if mechanically induced surface amorphization is compound dependent or a general phenomenon during media milling. Suspensions will be prepared with hard zirconium beads and softer cross-linked polystyrene beads and in combination to generate empirical data in the understanding of milling induced surface amorphization.
The model compounds will be selected from the drug crystallization classification system (Baird et al., 2010) to include compounds that is hard, intermedium and easy to crystallize as well as compound with high and low melting points to identify relevant characteristics that drives potential amorphization.
Problemformulering
Is mechanically induced surface amorphization during milling a general phenomenon across different drug compounds?
Metoder
Suspensions will be prepared using media milling by dual centrifugation and characterized by laser diffraction, differential scanning calorimetry (DSC) and HPLC .
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.
Reference
Baird JA, Van Eerdenbrugh B, Taylor LS. A classification system to assess the crystallization tendency of organic molecules from undercooled melts. J Pharm Sci. 2010;99(9): 3787–3806.