Development of probiotic orodispersible tablets using mucoadhesive polymers for buccal mucoadhesion

Abstract

Objective

Probiotic bacteria, such as different lactobacilli strains, have successfully been used to treat gingivitis and periodontitis or caries. By formulating probiotics as orodispersible tablet (ODT), the benefits of this dosage form could be utilized. Without any further measures, the probiotic bacteria will be eliminated too fast from the intended site of action, the oral mucosa. The use of mucoadhesive granules, composed of mucoadhesive polymer and probiotics, is a promising strategy to prolong the contact time between lactobacilli and oral mucosa without delaying disintegration.

Methods

Three common mucoadhesive polymers, anionic Carbopol 971P NF, nonionic Metolose 65SH50 and cationic chitosan were included into tablets either by direct compression (DC) or after granulation with the probiotics. Disintegration, mucoadhesion of the tablets, and storage stability of the probiotics were characterized.

Results

By incorporating a sufficient amount of polymer superior probiotic mucoadhesion could be achieved. All formulations based on granulated probiotics and mucoadhesive polymer fulfilled the Food and Drug Administration (FDA) acceptance level for disintegration of orodispersible tablets. These formulations exhibited excellent storage stability under refrigerated conditions over 30 months. Interestingly, ODTs including Carbopol 971P NF still proved superior mucoadhesion after long-term storage, whereas the mucoadhesive effect of Metolose 65SH50 and chitosan declined markedly.

Conclusions

The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.

Keywords:

• Mucoadhesion
• mucoadhesion testing
• buccal mucosa
• orodispersible tablets
• granulation
• hypromellose
• chitosan
• carbomer
• lactobacilli
• disintegration time

Acknowledgments

The authors would like to thank Grace GmbH & Co. KG for the provision of Syloid products, JRS Pharma GmbH & Co. KG for donation of Pruv, Roquette GmbH for supplying Pearlitol 100 SD and IMCD Deutschland GmbH & Co. KG for donating Avicel PH-112. Metolose 65SH50 was a gift from Shin‐Etsu Chemical Co., Carbopol 971P NF from Lubrizol Deutschland GmbH and chitosan food grade from Harke Pharma GmbH. Flavour was provided by Symrise AG and probiotics by Probi AB.

Disclosure statement

In accordance with Taylor & Francis policy and our ethical obligation as researchers, we are reporting personal fees and grants from Symrise AG. The stability study was performed at Symrise AG. In addition, the authors have a patent EP 3141242 pending. The funders had no role in the design of the study, in the analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Ethical approval

Porcine buccal mucosa was received from the department of experimental medicine of the University Hospital Tuebingen, where the pigs were sacrificed in the course of experiments, that had been approved by the ethics committee of the University Hospital Tuebingen. The buccal tissue was isolated directly after the death of the animals. Furthermore, porcine buccal mucosa was supplied by a local butcher (Grießhaber, Oeschingen, Germany) and the tissue was isolated immediately after the pig’s slaughter. The Department of Pharmaceutical Technology is registered for the use of animal products at the District Office of Tuebingen (registration number: DE 08 416 1052 21).