Development and pharmacological evaluation of floating drug delivery system of Tolbutamide

Abstract

The floating drug delivery system (FDDS) is the most practical swelling and expanding, polymeric bioadhesive, high-density, and modified-shape method. The study created and tested floating Tolbutamide microspheres to prolong medication release. Tolbutamide -loaded microspheres (E1-E9) of EC: HPMC (5, 100, and 4000 cps) were synthesised employing polymer ratio, drug concentration, emulsifier concentration, and stirring speed. The formulations were examined for SEM, FTIR, in-vitro buoyancy, yield, entrapment efficiency, and drug release. Optimised formulation release data from all four batches was fitted to mathematical models to establish release mechanism.

 All metrics for A2 formulation (EC: HPMC 5cps 1:2) were best, hence stability and in- vivo experiments were done. Stability at normal, rapid, and cold temperatures is studied for six months. Physical appearance, size, SEM images, buoyancy, residual drug content, and release were unchanged. In radiographic studies of barium sulfate-loaded A2 formulation floating, rats showed a mean stomach residency of almost 6 hours. In alloxan-induced diabetic rats, optimised formulations E2 and A2 (4mg/kg body weight dose of pure drug) were compared to normal, diabetic control, and pure drug for antidiabetic activity at various time intervals A2 was more effective than E2 against diabetes. After 15 days of administration, the formulation significantly maintains glucose levels (p<0.01). After 15 days of the antidiabetic study, liver, pancreatic, heart, and kidney histology were done. Control, diabetic, pure drug, and formulation (E2 & A2) histology were compared. Microscopic studies showed that optimised formulations similar to pure medicine reduced and reversed alloxan-induced severe hepatic, renal, pancreatic, and cardiac lesions. Extended release and lower dose frequency may increase Tolbutamide patient compliance with A2.