The Impact of Polymers in Amorphous Solid Dispersion on the Bioavailability of Sulfonylureas and Meglitinides

Diabetes mellitus (DM) represents a major and growing global health challenge. Among antidiabetic medications, sulfonylureas and meglitinides remain clinically relevant insulin secretagogues for the management of type 2 DM (T2DM). However, many drugs in these classes belong to Biopharmaceutics Classification System (BCS) Class II, which are characterized by low aqueous solubility and high membrane permeability. These physicochemical constraints result in slow dissolution, variable oral absorption, suboptimal bioavailability and inadequate glycemic control. Converting drugs into their amorphous form can enhance solubility and dissolution; however, amorphous drugs are inherently unstable and prone to recrystallization, limiting their practical use. Amorphous solid dispersion (ASD), which incorporates poorly soluble antidiabetic drugs into a polymeric matrix, offers a promising strategy to overcome these limitations. The polymeric carrier stabilizes the drug in its high-energy amorphous state, improving solubility, dissolution, and ultimately, bioavailability. In ASD systems, drug molecules are dispersed within the polymer matrix at the molecular level, forming extremely fine dispersion domains that may be even smaller than conventional nanoparticle systems, thereby enhancing apparent solubility and dissolution. This review provides a comprehensive overview of ASD applications in antidiabetic therapy, discussing the principles of ASD, commonly used polymeric carriers, fabrication methods, and recent in vitro and in vivo findings. Studies consistently show that ASD formulations of antidiabetic drugs such as glimepiride, repaglinide, gliclazide, gliquidone, and glyburide enhance insulin secretion and contribute to more effective glycemic control, showing the potential of ASD in improving the therapeutic performance of poorly soluble antidiabetic agents. By enhancing solubility, stability, and bioavailability, ASD technology holds significant promise for developing more potent and effective antidiabetic therapies, ultimately supporting better patient care and addressing the global burden of diabetes mellitus.