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

Diah Lia Aulifa,1 Tribuana Tungga Dewi Wansha Wibisono,1 Jahraema Deagustia Ningsih,1 Gabriel Daendya Amalia Bintang Christy,1 Dwi Sekar Pertiwi,2 Hilman Maulana Praja,2 Amirah Mohd Gazzali,3 Salma Amaliah,2 Arif Budiman2 1Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia; 3Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, MalaysiaCorrespondence: Arif Budiman, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia, Email arif.budiman@unpad.ac.idAbstract: 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. ASD enhances sulfonylureas/meglitinides dissolution, bioavailability, insulin release and glucose control.The diagram illustrates the process involving amorphous solid dispersion (ASD) of sulfonylureas/meglitinides. It begins with ASD, leading to an improved dissolution profile shown in a graph with dissolution percentage on the y-axis and time on the x-axis. The graph compares pure drug and ASD, indicating higher dissolution for ASD. Next, improved bioavailability is depicted with a graph showing Cmax and AUC (Area Under Curve) for pure drug and ASD, with ASD having higher values. This process results in increased insulin secretion and decreased blood glucose levels, as indicated by the final icons.