Introduction: Type 2 diabetes mellitus requires long-term pharmacotherapy; however, traditional oral antidiabetic agents suffer from low absorption, gastrointestinal side effects, and poor patient compliance. Transdermal nanofiber-based systems offer a promising alternative by enabling sustained release and improved permeation. This study aimed to develop and evaluate a dual-drug nanofibrous scaffold for enhanced transdermal delivery of Metformin hydrochloride and Sitagliptin phosphate. Methods: Dual-drug-loaded nanofibers were fabricated using electrospinning with polyvinyl alcohol and Eudragit RS100 as polymer matrices. A response surface methodology-based central composite design was employed to optimize polymer concentration and flow rate. The optimized nanofibers were characterized for morphology, entrapment efficiency, drug content, tensile strength, wettability, and stability using FESEM, FTIR, DSC, and physicochemical analyses. In vitro release and ex vivo permeation studies were performed using Franz diffusion cells and rat skin. Results: The optimized formulation exhibited uniform, bead-free nanofibers with consistent thickness (342 μm), high entrapment efficiency (92.4 %), and satisfactory mechanical strength. In vitro drug release demonstrated sustained delivery, achieving 95.9 % cumulative release over 12 hours. Ex vivo permeation showed superior transdermal flux (1.76 mg/cm²/hr) compared with single-drug formulations. FTIR and DSC confirmed drug–excipient compatibility, while stability studies indicated physicochemical stability under accelerated and intermediate conditions for three months. Discussion: The dual-drug nanofibrous scaffold enhanced drug loading, release modulation, and skin permeation, addressing limitations of oral therapy and supporting improved therapeutic performance. Conclusion: The developed Metformin–Sitagliptin nanofiber transdermal system offers a promising controlled-release platform with enhanced permeation and potential to improve glycemic management and patient compliance in type 2 diabetes.
Kapase et al. (Wed,) studied this question.