Locust bean gum glutarate nanocomposite hydrogel microspheres of gliclazide: Optimization by box-Behnken design and preclinical evaluation of anti-diabetic efficacy

Abstract

In this study, carboxymethyl locust bean gum was synthesized and nanocomposite hydrogel microspheres (GHMs) of gliclazide were produced based on nanosilicate reinforcement and aluminium-ion driven gelation process, followed by covalent crosslinking with glutaric anhydride (GA). The effect of three independent variables (polymer and GA concentration, incubation time) on the drug entrapment efficiency (DEE%) and percent drug release at 8 h, was optimized using Box-Behnken design. The highest DEE (%) and lowest drug release was achieved at the following optimized conditions: polymer (2.43 %), GA (0.34 %), and incubation (27 min). The nanoscilicate-enriched matrix provided a maximum of 75.13 % DEE, 92.33 % gel fraction, and excellent flowability. The optimized microspheres had virtually spherical morphology, according to FE-SEM analysis. FTIR study indicated a hydrogen bonding interaction between the drug and other formulation components. X-ray and DSC measurements suggested that the crystallinity of the drug decreased following integration into the matrix. The optimized GHM demonstrated anomalous diffusion of gliclazide in simulated gastrointestinal fluids for 12 h without disintegration. In streptozotocin (50 mg/kg BW)-induced diabetic rats, the optimized formulation diminished blood glucose level by about 72 % in 12 h. Thus, the nanocomposite GHMs created by combining nanosilicate with GA had an outstanding potential for long-term control of diabetes.