Low-Temperature Vacuum Spray Drying of Live Biotherapeutic Products : Formulation, Process Development and Data-Driven Analysis Using Probiotic Bacteria

Abstract

Low-temperature vacuum spray drying (VSD) is a potential drying approach for probiotic and live biotherapeutic product (LBP) formulations. This thesis investigated VSD for Limosilactobacillus reuteri DSM 17938 as a model probiotic strain, with the aim of identifying a feasible lab-scale operating window and using data-driven analysis to support process understanding.
Sucrose–maltodextrin formulations were processed using a Pilotech YC-2000 vacuum spray dryer under varied chamber pressures, inlet temperatures, and formulation compositions. The dried powders were characterised by outlet temperature, water activity, moisture content, powder recovery, particle morphology, particle size distribution, and bacterial viability. Bacterial viability was assessed by CFU counting before drying, after drying, and after 18 days of room-temperature storage. Empirical and machine-learning-assisted models were also applied to explore relationships between process variables, powder properties, and bacterial survival.
Across the bacteria-containing batches, outlet temperature ranged from 38.6 to 65.8℃, water activity from 0.145 to 0.272, and after-drying viability from approximately 3% to 31%. Higher outlet-temperature conditions generally reduced water activity but were associated with greater viability loss, whereas milder drying improved after-drying viability but did not always produce the lowest water activity. Batch 0316A, produced at 60 kPa, 80℃ inlet temperature, and a 90:10 sucrose:maltodextrin ratio, showed the most favourable overall performance, with approximately 26% after-drying viability, 81% storage retention, and 21% final survival.
Data-driven analysis supported this operating-window interpretation. Outlet temperature was described by an empirical linear model, water activity was analysed using Ridge regression, and after-drying viability was explored using Random Forest modelling. The modelling results indicated that bacterial survival was strongly linked to the outlet-temperature-related drying state, but remained exploratory due to the limited dataset size.
Overall, this study demonstrates that low-temperature VSD can produce L. reuteri-containing powders with measurable viability after drying and short-term storage, and identifies a promising process–formulation region for further optimisation of probiotic and LBP drying processes.

Popular Abstract

Can Good Bacteria Survive a Drying Storm?
Imagine a future medicine that contains living bacteria. These bacteria are the active part of the product and may help support health or even treat disease. But this raises a practical question: how can we make a medicine when the living cells themselves must survive the process?
One possible answer is to turn the bacteria into a dry powder. A powder is easier to handle than a liquid and can be used in forms such as capsules or mixtures. But there is a problem: drying is harsh. Drying takes away the water that living cells need. It is a bit like asking a fish to live outside water. If the drying is too harsh, the bacteria may be weakened or die.
This project studied whether a gentler drying method could help. The method is called low-temperature vacuum spray drying. In simple terms, a liquid containing bacteria is sprayed into tiny droplets and dried into powder. By lowering the pressure inside the drying chamber, water can evaporate at a lower temperature. This means the process may be less damaging than ordinary hot drying.
The main challenge was to find the right balance. If the drying process is too strong, the powder becomes drier, but more bacteria die. If the process is too gentle, more bacteria survive at first, but the powder may still contain too much available water, which can make storage more difficult. A good process therefore needs to protect the bacteria while still producing a stable powder.
In the experiments, probiotic bacteria were mixed with protective sugar-based ingredients and dried under different conditions. The dried powders were then tested to see how many bacteria survived after drying and after short-term storage. The results showed that the bacteria could survive the process, but the drying conditions made a clear difference. The best outcome was not simply the driest powder or the mildest process. Instead, it came from a middle-ground condition that balanced bacterial survival and powder stability.
This work shows that low-temperature vacuum spray drying is a promising route worth improving. With further optimisation, this type of process could help make future live bacterial products faster to manufacture, easier to store, and more practical to use.

• author: Xu, Chengxi
• supervisor: Anna Fureby
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM06 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• keywords: vacuum spray drying, probiotics, live biotherapeutic products, limosilactobacillus reuteri, bacterial viability, water activity, process development, data-driven analysis, pharmaceutical formulation
• language: English
• id: 9230559
• date added to LUP: 2026-06-04 12:33:06
• date last changed: 2026-06-04 12:33:06