New in-situ gelling biopolymer-based matrix for bioavailability enhancement of glimepiride; in-vitro/in-vivo x-ray imaging and pharmacodynamic evaluations

摘要

Glimepiride (Gmp) a third generation of sulphonylurea is a weakly acidic hypoglycemic drug that belongs to Biopharmaceutical Classification System (BCS) class II. It suffers from poor solubility as well as erratic and variable therapeutic effect. The authors investigated the feasibility of utilizing two nontoxic and biodegradable biopolymers (casein (CA) and chitosan (CT)) as a new in-situ gelling tablet matrix to circumvent this limitation. Both polymers in different ratios were combined with constant dose of the drug and compressed by direct compression to produce constant weights of different tablet matrices. Basic tromethamine (Tris) was also included in each matrix as a pH modifier. Swelling indices, rheological properties of the swollen matrices, and their in-vitro drug release in simulating gastric fluid were assessed. The higher the ratio of casein in the tablet matrix, the lower its swelling index and the higher its viscosity indicate a shear thickening property. Intuitively, zero order drug diffusion in 0.1 N HCl prevailed for more than 8 hours from this gelled matrix. Both reduction of blood glucose level up till 11 hours and x-ray imaging of the selected tablets in the GIT of rabbits correlated well with the shear thickening properties. These findings propose a new stable, simple and affordable price matrix with large versatility.