Diploma Work 30 hp, AstraZeneca Gothenburg

Start: August 2017

Titel: Which molecules end up on the surface of spray-dried particles?

We have recently been developing milligram scale methods for measuring relevant chemical/material properties of drug molecules/crystals. In 2016, an intern developed a novel milling method combined with surface analysis to categorize the relative tendencies of various molecules to stick to a lactose surface rather than to themselves. The surface analysis method was TOF-SIMS (time-of- flight secondary ion mass spectrometry). Lactose was chosen because of its importance as an excipient within inhalation formulation. Those molecules which favored sticking to themselves to sticking to lactose could be said to have a high cohesive-adhesive balance. The method was reproducible and showed remarkable grouping of the degree of coating results. That is, the 19 molecules had low, medium, or high levels of coating of lactose with no molecules between these levels. Work is ongoing to correlate these groupings with the molecules’ chemical or crystalline structure.

This new diploma student project is a continuation of the theme of milligram scale methods for measuring practical chemical properties of molecules. Again the tendencies of various test molecules to coat a surface will be analyzed with TOF-SIMS. This time the surface will not be lactose, and the coating will not be applied by collisions in a mill. The surface will be the excipient surface of spray-dried particles (or spin-coated films). [Spin-coated films can simulate spray-dying because of the fast drying time, and spin-coating may be easier to do.] The coating will occur as the test molecule moves to or drops out onto the excipient surface during drying. [Roughness of spin-coated films as a function of different test molecules may also be measured by AFM (atomic force microscopy).]

We will take a base form of excipients appropriate for spray-drying and vary the test molecule. The degree to which the test molecule covers the surface of spray-dried particles is of great interest because this affects particle adhesion which affects agglomeration which in turn affects powder flow both in filling of inhalation devices and in the dispersion of the particles during inhalation. (Non-dispersed agglomerates larger than ~5µm will not be successfully delivered to the lungs.)

Test molecules from various classes of molecules will be chosen to span the space of size, hydrophobicity, and other chemical structure metrics. To expand the chemical space, non-drug test molecules will also be considered. We will choose between a small-scale commercial spray-dryer, a custom made micro-spray dryer, an inkjet spray-dryer, and spin-coating. Additionally, we may investigate the surface composition versus particle size (which inversely correlates to the drying rate). And the surface stability with time, temperature, and humidity of the spray-dried or spin-coated films can also be studied. This could include stability of the surface coverage, chemical stability of the test molecule, or roughness stability (for spin-coated films whose roughness could be easily measured by AFM).

Last day for application; 2017-05-15

For questions: please contact Mark Nicholas; 031-776 10 00