Recent Advances in Glimepiride Solubility Improvement: A Focus on Formulation Technologies A Narrative Review

Valentina Fiftianingrum,1,2 Iyan Sopyan,1 Sandra Megantara,3 Cecep Suhandi1 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 2Master Program of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 3Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, IndonesiaCorrespondence: Iyan Sopyan, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia, Email i.sopyan@unpad.ac.idAbstract: Glimepiride, a second-generation sulfonylurea used in the management of type 2 diabetes mellitus, is classified as a Biopharmaceutics Classification System (BCS) Class II drug. Its severely limited aqueous solubility (< 0.004 mg/mL at pH < 7) leads to erratic and insufficient oral bioavailability, preventing consistent attainment of therapeutic plasma levels. This narrative review analyzes literature published between 2015 and 2025 from databases including PubMed, Scopus, and ScienceDirect. This review critically examines advanced formulation strategies designed to enhance Glimepiride’s dissolution rate and aqueous solubility. Approaches are grouped into two categories: (1) solid-state modifications—including solid dispersions, co-crystals, and inclusion complexes—which alter the drug’s solid state properties, with co-crystals reported to improve in vivo absorption by up to 2.66-fold; and (2) nanoparticle-based systems such as nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS), which increase surface area through particle size reduction, with nanosuspensions achieving up to a 6.58-fold solubility enhancement. The advantages and limitations of these technologies are evaluated to identify the most promising strategies for improving glimepiride’s therapeutic performance and supporting better patient outcomes.Keywords: glimepiride, solubility enhancement, BCS class II, solid-state modification, nanoparticle systems