Novel self-floating tablet for enhanced oral bioavailability of metformin based on cellulose.

ABSTRACT

Metformin has several problems such as low bioavailability, short half-life, and narrow absorption window, sustained and site-specific drug delivery system is required. Floating drug delivery systems are very useful to achieve these purposes. However, conventional floating systems have several limitations; lag time, a high proportion of excipient in the tablet, using non-biocompatible excipient, and requirement of a complicated procedure. To overcome these obstacles, we developed a hollow-core floating tablet (HCFT). The HCFT immediately floated in pH 1.2, 4.0, 6.8 medium, and even distilled water. The floating duration time of HCFT was>24 h. From the in vitro release study, it was confirmed that HCFT showed the sustain release profile of metformin for 12 h. Water uptake and matrix erosion were evaluated for predicting the buoyancy and drug release kinetics of HCFT in the body. Factor analysis was applied to optimize the formulation. There were significant (p < 0.05) differences in metformin plasma concentration of 4 h and 6 h between two groups. Compared with Glucophage® XR, the relative bioavailability of metformin HCFT was 123.81 ± 3.52%. The X-ray imaging of optimized formulation revealed that HCFT was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention for>6 h. Consequently, all the findings indicate that HCFT could be an effective gastric retention system and applied extensively to other drugs with narrow absorption windows.