# Modeling of physical-mechanical and microbiological properties of tablets made of complex fluidized bed granules containing living yeast cells using common mixing rules

## TL;DR

This study models how to make tablets with live yeast cells by combining different ingredients and predicting their physical and microbiological properties.

## Contribution

The paper introduces a method to predict tablet properties and yeast survival using mixing rules and extends a model for better accuracy.

## Key findings

- Volume-weighted mixing rules accurately predicted compressibility for two of three carriers.
- Lactose and microcrystalline cellulose improved yeast survival during granulation.
- Porosity reduction during compaction significantly affects yeast survival.

## Abstract

In order to administer probiotic microorganisms effectively, suitable dosage forms and production methods are required. These must be geared towards maintaining viability, which is essential for the health-promoting properties. In earlier studies, fluidized bed spray granulation with subsequent further processing into tablets showed promising results. The physical-mechanical and microbiological tablet properties were found to depend on the excipient. The occurrence of advantageous synergies was investigated by combining different excipients during granulation. Since mixed properties were largely observed, volume-weighted mixing rules were applied to predict the compressibility, compactibility and tabletability of single, binary and ternary carrier granules based on the tableting of the non-granulated excipients. For one of the three carriers investigated, the common model had to be extended by a correction term, whereas for the other two carriers, a very good prediction could be made directly. Similarly, the survival of the microorganisms in single-carrier granules was modeled and used to predict survival in binary and ternary mixed granules. In contrast, the prediction of the microbiological survival was less accurate. Overall, the combination of lactose and microcrystalline cellulose turned out to be overall advantageous for survival. However, this is due to the especially high survival during granulation and not during tableting. The previously identified dependence of survival on porosity reduction was confirmed for the more complex formulations and could be the basis for further development of models to predict survival during compaction.

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