A Review of Rational Design of Once-Daily Glipizide Sustained-Release Matrix Tablets

Abstract

Type II diabetes mellitus affects over 537 million adults globally, with glipizide remaining a widely prescribed second-generation sulfonylurea. Despite 100% oral bioavailability, glipizide exhibits a short elimination half-life of 2–4.7 hours, high plasma protein binding of 98–99%, and pH-dependent solubility, necessitating 2–3 times daily dosing. This dosing frequency causes peak–trough plasma fluctuations, increasing hypoglycemia risk and reducing patient compliance. Sustained-release (SR) matrix tablets provide a rational solution by maintaining therapeutic plasma concentrations for 12–24 hours with once-daily dosing. This review critically evaluates the formulation and evaluation of glipizide SR matrix tablets, focusing on the mechanistic roles of HPMC K100M and Eudragit RSPO, excipient functionality (advantages and disadvantages), formulation optimization strategies, and recent advances from 2015–2025. Optimized HPMC K100M: Eudragit RSPO blends at 2:1 ratios combined with a 1:1 Lactose: DCP ratio achieve zero-order release over 12–16 hours with f₂ >50 against marketed Glucotrol XL. Challenges of burst release, over-lubrication, and IVIVC establishment are discussed.

Keywords: Glipizide; Sustained release; Matrix tablets; HPMC K100M; Eudragit RSPO; Type II diabetes; Hydrophilic matrix.