Glutaric Anhydride as Additive for the Development and Optimization of N‐Acetyl‐L‐Cysteine‐Conjugated Mucoadhesive Galactomannan Microspheres for Extended Release of Glimepiride

ABSTRACT In this study, locust bean gum was chemically functionalized to its carboxymethyl derivative and subsequently N‐acetyl‐L‐cysteine was conjugated to impart the polymer gel‐forming and mucoadhesive characteristics, respectively. The introduction of functional groups was confirmed by estimating degree of O ‐carboxymethylation, degree of thiolation, degree of esterification, and FTIR spectroscopy. The modified polymer hydrogel microspheres of glimepiride were prepared via ionic and covalent crosslinking using glutaric anhydride (GA) using a 3‐factor‐3‐level Box–Behnken design. FESEM analysis revealed that both GA‐treated and ‐untreated microspheres were spherical in shape, but the GA treatment altered the surface texture of microspheres. FTIR findings revealed a slight drug‐polymer interaction. The drug was not entirely converted into an amorphous state during entrapment, according to thermal and x‐ray analyses. The optimized microspheres had about 85% drug entrapment efficiency. The GA‐untreated microspheres swelled and disrupted following a change in pH from pH 1.2 to pH 6.8 after 4 h, releasing about 70% drug. The GA‐treated thiolated microspheres progressively expanded, released roughly 50% drug in 12 h and provided about 1.5‐fold higher mucoadhesive strength. Korsmeyer‐Peppas modeling dictated an anomalous drug diffusion mechanism. Overall, the GA, a green additive, appeared suitable in modulating the drug release rate from the microspheres under gastrointestinal pH simulation, thereby offering potential for diabetes management.