Design And Development Of Glimepiride Sustained-Release Implants For Long-Term Glycemic Control

Abstract

Objective: To design and develop sustained-release (SR) glimepiride implants enabling long-term glycemic control with minimized burst release and improved adherence.

Methods: Biodegradable PLGA-based in situ forming implants were engineered with solvent-induced phase inversion, using N-methyl-2-pyrrolidone as the primary solvent and polyethylene glycol as a plasticizer to modulate matrix porosity and initial drug efflux. A response-surface design optimized polymer concentration, plasticizer level, and co-solvent ratio to balance burst control and sustained kinetics. Formulations were characterized by SEM, in vitro release profiling over 28 days, and in vivo pharmacokinetics/pharmacodynamics in diabetic rodent models versus oral glimepiride.

Results: Increasing PLGA and PEG content reduced surface porosity and attenuated the initial burst while sustaining release, achieving near-zero-order kinetics post-induction. Optimized implants curtailed 2–24h burst and provided depot activity for up to 14 days in vivo, maintaining plasma levels comparable to safe exposures from marketed tablets while prolonging glucose-lowering effects. Embedding glimepiride in nanoparticulate/triblock matrices within PLGA systems further refined release control and depot performance. Design principles and strategies align with contemporary advances in PLGA implant engineering to mitigate burst and enhance completeness of release.

Conclusion: Glimepiride SR implants based on optimized PLGA in situ systems offer a feasible depot approach for extended glycemic control, with controlled burst, sustained therapeutic exposure, and potential to improve adherence and outcomes in type 2 diabetes.