Exorbitant Drug Loading of Metformin and Sitagliptin in Mucoadhesive Buccal Tablet: In Vitro and In Vivo Characterization in Healthy Volunteers

The aim of the proposed study is to develop a mucoadhesive buccal delivery system for the sustained delivery of metformin (MET) and sitagliptin (SIT) against diabetes mellitus (DM) with improved bioavailability. Polymeric blend of Carbopol (R) 940 (CP), agarose (AG) or polyvinylpyrrolidone K30 (PVP) as mucoadhesive agents in formulations (R1-R15) were compressed via the direct compression technique. Tablets were characterized for solid state studies, physicochemical and in vivo mucoadhesion studies in healthy volunteers. Outcomes did not reveal any unusual peak or interaction between the drugs and polymers in the physical mixture through Fourier Transform Infrared Spectroscopy (FTIR) and DSC analysis. The mucoadhesive blend of CP and PVP was superior compared to other blends. The formulation R4 revealed exorbitant loading of drugs with complete drug release for 6 h with ex vivo mucoadhesive strength and time of 26.99 g and 8.1 h, respectively. It was further scrutinized to evaluate it as an optimized formulation where it was found to be stable for up to 6 months. The formulation R4 depicted Korsmeyer-Peppas model and first-order mode of release correspondingly for SIT and MET. Moreover, it showed hemocompatibility, biocompatibility and stability with non-significant changes in the dissolution profile. Overall, the CP blend with PVP was found appropriate to yield the desired release coupled with the optimized mucoadhesive properties of the buccal tablets, ensuring sufficient pharmaceutical stability.

Automated summary

The aim of this study was to develop a buccal delivery system with mucoadhesive properties for sustained release of metformin and sitagliptin in the treatment of diabetes mellitus. The use of Carbopol 940, agarose, and polyvinylpyrrolidone K30 as mucoadhesive agents in tablet formulations resulted in favorable mucoadhesive properties. Formulation R4 showed complete drug release within 6 hours, with a mucoadhesive strength of 26.99 g and a mucoadhesive time of 8.1 h in ex vivo studies. The CP and PVP blend demonstrated stability for up to 6 months. Overall, the CP and PVP blend was found to be appropriate for achieving the desired release and mucoadhesive properties in buccal tablets.