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

Abstract

The administration of living microorganisms is of special interest, with regard to probiotic microorganisms providing health benefits to the patient. Effective dosage forms require the preservation of microbial viability until administration. Storage stability can be improved by drying, and the tablet is an especially attractive final solid dosage form due to its ease of administration and its good patient compliance. In this study, drying of the yeast Saccharomyces cerevisiae via fluidized bed spray granulation is investigated, as the probiotic Saccharomyces boulardii is a variety of it. Fluidized bed granulation enables faster drying than lyophilization on the one hand and lower temperatures than spray drying on the other hand, which are the two predominantly used techniques for life-sustaining drying of microorganisms. Yeast cell suspensions enriched with protective additives were sprayed onto the carrier particles of common tableting excipients, namely, dicalcium phosphate (DCP), lactose (LAC) and microcrystalline cellulose (MCC). Different protectants, such as mono-, di-, oligo- and polysaccharides, but also skimmed milk powder and one alditol, were tested; as they themselves, or chemically similar molecules, are known from other drying technologies to stabilize biological structures such as cell membranes, and thus, improve survival during dehydration. With the combined use of trehalose and skimmed milk powder, survival rates were 300 times higher than without the use of protective additives. In addition to these formulation aspects, the influence of process parameters such as inlet temperature and spray rate were considered. The granulated products were characterized regarding their particle size distribution, moisture content and the viability of the yeast cells. It has been shown that thermal stress on the microorganisms is especially critical, which can be reduced, for example, by reducing the inlet temperature or increasing the spray rate; however, formulation parameters such as cell concentration also influenced survival. The results were used to specify the influencing factors on the survival of microorganisms during fluidized bed granulation and to derive their linkages. Granules based on the three different carrier materials were tableted and the survival of the microorganisms was evaluated and linked to the tablet tensile strength achieved. Using LAC enabled the highest survival of the microorganisms throughout the considered process chain.

Oral pharmabiotic tablet formulations

“…As preservatives, starch, lactose, inulin, dextran, sorbitol, trihalose, two different ratios of milk powder, maltrodextrin, xylose and two different ratios of trihalose + milk powder mixture were compared, respectively. It was observed that trihalose + milk powder mixture used in equal proportions had a significant effect on bacterial viability compared to tablets without preservatives (89). The same research group examined the parameters in the tablet pressing process of the granules of S. cerevisiae formed by spray drying technique.…”

Microbial Preservation and Contamination Control in the Baking Industry

“…The data analysis resulted in an optimal operating point at a loading rate of 350 kg/h and temperatures between 29 and 33 • C as well as high yeast cell viability of up to 76%, which was 27% higher than the viability of the yeast in the normal operating conditions of the plant. According to Vorländer et al [79], fluidized bed application enables faster drying than lyophilization, on the one hand, and lower temperatures than spraydrying, on the other hand, the two predominantly used techniques for life-sustaining drying of microorganisms. In this study, the authors showed different protectants for S. cerevisiae, such as mono-, di-, oligo-and polysaccharides, but also skimmed milk powder and one alditol, as they, or chemically similar molecules, are known from other drying technologies to stabilize biological structures such as cell membranes, and thus, improve survival during dehydration.…”

“…According to Wirunpan et al [84], the survival rate of L. lactis 1464 in shrimp feed pellets ranges from 89.54% to 96.87% at 80 and 50 • C, respectively. The survival rate in the fluidized bed drying process is intrinsically related to process temperature, drying time, and cell concentration [79]. Wu et al [85] evaluated the optimization of the process parameters using a fluidized bed to dry and encapsulate L. brevis RK03; the authors achieved a survival rate of 95% using casein and whey protein as carriers.…”

10. Literature Review of Research and Development of Probiotic Tablets

“…Conduct stability testing to assess the viability of probiotic strains throughout the product's shelf life. Assess the influence of temperature, humidity, and other environmental factors on probiotic viability to select the most suitable strain for the design [12].…”

“…Conversely, consolidation time did not exert a significant impact on the tablet quality attributes considered. Given the negligible changes in survival rates relative to tensile strength (due to opposing yet compensatory influences on porosity), high production speeds could be employed for granule tabletting without compromising viability, as long as tablets with equivalent tensile strength are produced [28,29].…”