Does tablet shape and height influence survival of fluidized bed-granulated living microorganisms during compaction?
Abstract
The provision of effective probiotic formulations requires gentle processing to maintain the viability of the probiotic microorganisms, which is essential for their health-promoting effects. The drying of microorganisms by fluidized bed spray granulation and subsequent processing of the granules into tablets has proven to be a promising process route in previous studies of the same authors. In these, the influence of various factors was considered using cylindrical tablets with a diameter of 11.28 mm and a mass of 450 mg.
These flat tablets are unpleasant to ingest and other tablet geometries should be considered for administration of probiotics but to date, no studies exist on the influence of geometric factors of the tableting tool and of the tablets on the survival of microorganisms. To address this aspect, the survival of Saccharomyces cerevisiae during the production of flat, round tablets with different tablet masses and thus heights as well as differently shaped convex tablets is determined and related to the physical-mechanical tablet properties to derive process-structure-property relationships.
It turned out that higher tablet heights were advantageous regarding microbial survival and mechanical strength which is attributed to a lower elastic recovery. However, the use of differently shaped tools had a smaller influence on microbiological and mechanical tablet properties since the global tablet porosity was hardly affected.
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Materials
2.1. Granules containing living microorganisms
Granules containing viable cells of the yeast Saccharomyces cerevisiae (fresh yeast from Deutsche Hefewerke, Nürnberg,Germany) on the basis of dicalcium phosphate (DCP, DI-CAFOS A150, kindly provided by Chemische Fabrik Budenheim KG, Budenheim, Germany), lactose (LAC, Granulac 70, kindly provided by MEGGLE GmbH & Co. KG, Wasserburg am Inn, Germany) or microcrystalline cellulose (MCC, Vivapur 102, kindly provided by J. Rettenmaier & Söhne GmbH + Co KG (JRS Pharma), Rosenberg, Germany) were produced in a previous study (Vorländer et al., 2023b) and used for the present study. S. cerevisiae serves as a model organism in this study due to its similarity to the probiotic yeast Saccharomyces cerevisiae subsp. boulardii (Edwards-Ingram et al., 2007) and the easy availability of fresh cells with batch-to-batch consistency. Beside the microorganisms and water, the granulation liquid consisted of trehalose and skimmed milk powder as additives to protect the cells during drying. 825 g of the suspension with a solid mass of 310 g (50 % of cell dry weight (CDW), 25 % of trehalose and 25 % of skimmed milk powder) were sprayed on 1 kg of DCP, LAC and MCC, respectively, in a fluidized bed (Solidlab 2, Syntegon Technology GmbH, Waiblingen, Germany). A more detailed description could be found elsewhere (Vorländer et al., 2023a; Vorländer et al., 2023b). Survival during granulation depended on the carrier material and was 19.7 ± 0.9 % with DCP, 13 ± 2 % with LAC and 10.3 ± 0.2 % with MCC. Particle size distribution are shown in of the carrier particles and granules (Fig. S1) was characterized by dynamic image analysis (QICPIC with GRADIS dispersing unit and VIBRI dosing unit, Clausthal-Zellerfeld, Germany). The analysis was repeated three times with a minimum of 100,000 particles analyzed each time.
2.2. Tableting
DCP, LAC, MCC and the corresponding yeast granules were compressed to tablets using a compaction simulator (Styl’One evolution, MEDELPHARM, Beynost, France). To reduce ejection forces, a suitable amount of magnesium stearate (MgSt, MAGNESIA GmbH, Lüneburg, Germany) as lubricant was added and dispersed with a tumbling mixer (TURBULA, Willi A. Bachofen AG, Muttenz, Switzerland) for 2 min at 49 min−1. Lubrication was necessary for pure DCP (1 wt.-% MgSt) and LAC (0.5 wt.-% MgSt) as well as for the both corresponding granules (both 0.5 wt.-% MgSt). Poor flow properties of MCC (ungranulated carrier material) required addition of 0.5 wt.-% of highly dispersed SiO2 (Aerosil 200, Evonik Industries AG, Essen, Germany) to ensure homogeneous die filling (mixed for 10 min at 49 min−1). The addition of MgSt was not necessary due to the low ejection forces that occur when tableting MCC or formulations with a high proportion of MCC like the MCC granules. A symmetrical, trapezoidal compression profile with a set consolidation time of 90 ms and a set dwell time of 20 ms was used for displacement-controlled compression.
Karl Vorländer, Lukas Bahlmann, Arno Kwade, Jan Henrik Finke, Ingo Kampen, Does tablet shape and height influence survival of fluidized bed-granulated living microorganisms during compaction?, International Journal of Pharmaceutics: X, Volume 9, 2025, 100332, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2025.100332.
