Optimizing the spray drying of Lactobacillus rhamnosus GG as an important step towards the development of successful pharmabiotics

Abstract: At present time, every hour 80 people die due to the consequences of antimicrobial resistance. A \u2018post-antibiotic\u2019 era threatens the global population, as warned by the World Health Organization (WHO). This has prompted the scientific world to search for alternative strategies to manage and prevent diseases. With the increasing awareness of the role that our human microbiome plays in health and disease, one of the strategies explored is the application of probiotics as a preventive and/or therapeutic agent for infectious diseases. Probiotics are defined as \u2018live microorganisms that, when administered in adequate amounts, confer a health benefit to the host\u2019 (Hill et al., 2014). The road to develop successful pharmabiotics, i.e. probiotics in pharmaceutical formulations, is very challenging. One of the key hurdles for formulators, is to keep the bacteria alive and active during a longer period of time (preferably up to several years). To enhance shelf-life stability, bacteria are dried, which decreases the available free water content, and this slows down the bacterial metabolism. Freeze drying is the commonly used method in the pharmaceutical industry to dry biopharmaceuticals, such as probiotics. However, in recent years, spray drying has been brought forward as a promising alternative to freeze drying. It is a cheap, fast, and continuous process, where the end products consist of a particulate powder. However, due to the high temperatures used during spray drying and the lack of sufficient long-term storage data (to date), the pharmaceutical industry is skeptical to implement this drying technology to process probiotics. Therefore, the goal of this research is to investigate if spray drying can be used to produce viable probiotics, which can be stored during a sufficient amount of time. Three protection strategies were investigated, namely, addition of protective agents, controlling the process parameters and pretreating the bacterial cells prior to spray drying. Noteworthy, promising results regarding long-term stability (for up to more than two years) were obtained with the addition of small disaccharides (like lactose and trehalose) and the presence of phosphates in the drying medium, even when storing at room temperature. Although, the road to develop successful pharmabiotics is still full of hurdles to overcome and problems to be solved, it can be concluded that an exciting future lies ahead for us and our friendly microbes