A Ph.D. position within formulation characterization focused on stability investigations of pharmaceutical suspensions is available at the Department of Physics, Chemistry, and Pharmacy in the pharmacy research group.  

Project background 

Terminal sterilization is the process of sterilizing a pharmaceutical product in its final container. Among various sterilization techniques, moist heat sterilization (autoclaving at 121°C) is the most widely accepted and validated method due to its proven microbial lethality, cost-effectiveness, and ease of implementation at scale- Other options are gamma radiation and E-beam. Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), strongly prefer terminal sterilization over aseptic manufacturing wherever feasible, as it offers a higher Sterility Assurance Level (SAL) and significantly reduces the risk of post-process contamination. 

Despite its advantages, terminal sterilization is not universally applicable. A significant limitation arises when drug substances or drug formulations are thermolabile, meaning they degrade either chemically or physically upon exposure to high temperatures. This is especially problematic for colloidal based formulations, such as suspensions intended for injection, which also cannot be sterile filtrated. Terminal sterilization of suspensions can lead to aggregation, hydrolysis, oxidation, Ostwald riepening or other chemical and physical degradation pathways. As a result, most marketed parenteral suspension products are manufactured using aseptic processing, where the drug and container are sterilized separately and then combined under aseptic conditions. Although effective, aseptic processing introduces significant operational complexity, requires extensive environmental controls, is more costly, and presents a higher risk of microbial contamination. 

To stabilize the inherently thermodynamic instable suspensions addition of surfactants to stabilize the formulation is often needed. These surfactants are commonly nonionic surfactants, such as polysorbates and poloxamers, which have cloud points below 121 °C, i.e. they will phase invert at autoclavation temperature. Older literature teaches us that the cloud point can be elevated by the addition of e.g. PEG400, PEG3350, and some lecithin’s. This was in a later study applied to suspensions with ethyl diatrizoate nanocrystalline suspensions that could be stream autoclaved if the media was added cloud point boosters to bring it to approximately 135 °C. Colleges from Pfizer have at conferences presented data suggesting that they occasionally see similar trend for some compound, however, slides have not been shared for further analysis.  

This project aligns closely with Quality by Design (QbD) principles, emphasizing risk assessment, process understanding, and robust design space development. A successful outcome of this project will provide pharmaceutical scientists with the tools to improve the physical stability of aqueous suspensions and if fully successful extend the applicability of terminal sterilization of parenteral suspensions thus improving product quality, regulatory compliance, and patient safety. By overcoming formulation barriers to terminal sterilization, this project has the potential to significantly impact the field of sterile pharmaceutical manufacturing, offering both clinical and economic benefits across the product lifecycle.  

Qualifications 

• We are looking for a candidate with a strong interest in working on the boundary between pharmacy, chemistry and physics focused on formulation and characterization of suspensions and solid materials. 

• The candidate will hold a M.Sc. in pharmacy, chemistry, physics, or closely related area. 

• Previous experiences with one or more of the following are considered an advantage: formulation design of suspensions, particle size characterization, XRPD, solid stage NMR, low energy Raman microscopy. 

• The candidate must be independent and fluent in English both orally and written.  

Application deadline: 26 deember at 23:59 hours local Danish time

Please see the full call, including how to apply, on sdu.dk