Along the Process Chain to Probiotic Tablets: Evaluation of Mechanical Impacts on Microbial Viability

Abstract

Today, probiotics are predominantly used in liquid or semi-solid functionalized foods, showing a rapid loss of cell viability. Due to the increasing spread of antibiotic resistance, probiotics are promising in pharmaceutical development because of their antimicrobial effects. This increases the formulation requirements, e.g., the need for an enhanced shelf life that is achieved by drying, mainly by lyophilization. For oral administration, the process chain for production of tablets containing microorganisms is of high interest and, thus, was investigated in this study. Lyophilization as an initial process step showed low cell survival of only 12.8%. However, the addition of cryoprotectants enabled survival rates up to 42.9%. Subsequently, the dried cells were gently milled. This powder was tableted directly or after mixing with excipients microcrystalline cellulose, dicalcium phosphate or lactose. Survival rates during tableting varied between 1.4% and 24.1%, depending on the formulation and the applied compaction stress. More detailed analysis of the tablet properties showed advantages of excipients in respect of cell survival and tablet mechanical strength. Maximum overall survival rate along the complete manufacturing process was >5%, enabling doses of 6 × 10 8 colony forming units per gram ( CFU g total − 1 ), including cryoprotectants and excipients.

Characteristics of Probiotic Preparations and Their Applications

“…Although tablets are not the preferred dosage form for probiotic preparations, the properties of tablets make them an important direction for probiotic drug development. In view of the adverse effects on the bioactivity of probiotics caused by compression and wet granulation methods, the general process for probiotic tablet formulation is to mix the powder with an excipient after a drying procedure and then press the tablets directly into shape [ 48 ]. However, processes such as drying, mixing and compression inevitably destroy a wide range of cellular and biologically active components of probiotics, which is a challenge that needs to be addressed in the design of probiotic tablets [ 49 ].…”

Effect of Process Parameters, Protectants and Carrier Materials on the Survival of Yeast Cells during Fluidized Bed Granulation for Tableting

“…Tablets have some major advantages, such as easy administration of exact doses, masking of any bad taste and odor of the microorganisms, and thus generally high patient acceptance. Therefore, this is often the delivery of choice for probiotics, even though compaction into tablets is a critical step for microbial viability [ 7 , 8 , 9 ].…”

“…In addition, the process is slow and investment and energy intensive. Although lyophilized yeast cells were also already tableted, an additional upstream comminution step was necessary, which was accompanied by an additional reduction in viability [ 9 ]. Furthermore, the mechanical strength of the tablets was comparatively low, so high compaction stresses had to be applied, which negatively affected the viability of the cells in the tablets.…”

Powder Processing in Pharmaceutical Applications—In-Depth Understanding and Modelling

“…The contributions in this Special Issue address powder processing in granulation [1,2], capsule filling [3], tableting [4][5][6][7], and along whole process chains [8], which powders mostly experience in industrial applications. Furthermore, articles span the application depths from scaling from lab to production scale [1,4] and transforming suspensions into dry products [2,8], over in-depth description of sub processes on rotary presses, which depend on powder properties [5][6][7], to statistical experimental design [1,3] and application of artificial neural networks [3].…”

“…A whole process chain from transfer of suspension to dry powder by freeze drying and comminution through a sieve over blending with tableting excipients to compaction is studied to evaluate the influence of these several process steps on the viability of microorganisms [8]. This study aiming at probiotic tablet formulations provides an approach to achieve a high survival rate of the microorganisms by the correct choice of excipients and process parameters.…”