Enabling Stable and Directly Compressible Probiotic Tablet Formulations with a Novel Co-processed Mannitol-Starch Excipient

This case study was presented at the 14th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 18 – 21 March 2024, Vienna, Austria:

INTRODUCTION

The growing interest in probiotic supplements is driven by the favorable effects on intestinal microbiota and contributions to the health of the host environment, many of which are backed by scientific studies.¹ Probiotic microorganism strains such as lactic acid bacteria and Bifidobacterium have a long history of safe use and confer various beneficial effects when ingested in appropriate concentrations. Chewable probiotic tablets are an attractive dosage form because of its convenience and the ease of administration and swallowability. However, the present challenge in probiotic tablet formulations is the maintenance of sufficient number of viable cells at the time of consumption.²

The ideal water activity (Aw) for probiotic microorganism survival is generally reported to be between 0.2 to 0.3.³ If the Aw of the microorganism is too low, the dehydrated state could cause the membrane lipids to be oxidized, leading to reduced viability. Conversely, if the Aw is too high, there is an increased risk of uncontrolled solubility and chemical reactions between organic compounds. As such, the selection of a low Aw excipient in a probiotic formulation is imperative for probiotic stability reasons. As a tableting excipient, it should exhibit good processability and confer a pleasant taste profile in the final formulation. PEARLITOL® ProTec co-processed mannitol-starch excipient was hence developed to meet these needs.

The objectives of this study were to characterize PEARLITOL^® ProTec and evaluate the stability of probiotic formulations comprising of PEARLITOL^® ProTec at the following stages: (i) post-tablet production and (ii) storage over 3 months.

RESULTS AND DISCUSSION

I. Characterization of PEARLITOL^® ProTec excipient

The appearance of PEARLITOL^® ProTec is shown in Figure 1, and the measured physical properties are listed in Table 1. PEARLITOL^® ProTec exhibited good flow properties based on the Carr’s Index and Hausner ratio. Furthermore, the low Aw and moisture content of PEARLITOL^® ProTec are important considerations with regards to the choice of a suitable filler excipient to be incorporated with probiotics, to ensure stability of the formulation.

II. Stability evaluation of probiotic tablet containing PEARLITOL^® ProTec

It is well understood that the compaction force has an impact on the viability of the probiotic, where a higher force typically results in a greater loss in viability. It has earlier been reported by Byl et al. that a certain level of elastic recovery is useful in safeguarding the viability of Lb. rhamnosus GG.2 Hence, the post-compaction viability was determined to understand the protective effect on the probiotic that could be conferred by PEARLITOL^® ProTec during compaction. As shown in Figure 2, the protection conferred by PEARLITOL^® ProTec was demonstrated even at higher compaction forces.

Regardless of the tablet compaction force employed or the storage condition, the tablet hardness (Figure 3), disintegration time (Figure 4), water activity (Figure 5) and water content (Figure 6) were well-maintained throughout the 3-months study duration.  The viability of Lb. rhamnosus was also evaluated, and the formulations stored in fridge condition demonstrated stability as expected. However, when the same formulations were stored in the ambient conditions, the decrease in viability for the Lb. rhamnosus neat powder was drastic as compared to those formulated with PEARLITOL^® ProTec (Figure 7).

CONCLUSION

It was demonstrated that the presence of PEARLITOL^® ProTec conferred protection to the formulation during compaction and on storage. With storage in ambient conditions, the viability counts could still be maintained at acceptable levels, which highlights the benefit of the low Aw PEARLITOL^® ProTec in the formulation.

Read the original article here

Source: Roquette, Carin Siow, Lesley Ooi, Kwan Hang Lam, Low Jeslyn, Bing Xun TAN, Probiotic Tablet with a Novel Co-processed Mannitol-Starch Excipient (roquette.com)

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