Department of Pharmaceutical Technology, Eberhard Karls University, Tuebingen, Germany.
Symrise AG, Holzminden, Germany.
Drug Dev Ind Pharm. 2020 Nov;46(11):1753-1762. doi: 10.1080/03639045.2020.1831013.
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.
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.
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.
The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.
益生菌，如不同的乳杆菌菌株，已成功用于治疗牙龈炎和牙周炎或龋齿。通过将益生菌制成口腔分散片（ODT），可以利用这种剂型的优势。如果不采取进一步的措施，益生菌将过快地从口腔黏膜这一预期作用部位被清除。使用由亲水性聚合物和益生菌组成的粘膜粘附颗粒是一种很有前途的策略，可以延长益生菌与口腔粘膜的接触时间，而不会延迟崩解。
本研究包含三种常见的粘膜粘附聚合物，阴离子 Carbopol 971P NF、非离子 Metolose 65SH50 和阳离子壳聚糖，分别通过直接压片（DC）或与益生菌造粒后加入片剂中。对片剂的崩解、粘膜粘附和益生菌的储存稳定性进行了表征。
通过加入足够量的聚合物，可以实现优越的益生菌粘膜粘附。所有基于造粒益生菌和粘膜粘附聚合物的配方均满足食品和药物管理局（FDA）对口腔分散片崩解的接受标准。这些配方在冷藏条件下储存 30 个月以上仍具有极好的储存稳定性。有趣的是，包含 Carbopol 971P NF 的 ODT 在长期储存后仍表现出优异的粘膜粘附性，而 Metolose 65SH50 和壳聚糖的粘膜粘附效果则明显下降。
本研究结果表明，Carbopol 971P NF 是益生菌粘膜粘附 ODT 最合适的聚合物。
