Fast-dissolving cyclodextrin nanofibers loaded with acetylsalicylic acid, paracetamol and caffeine combination for the pain treatment.

We developed a fast-dissolving nanofibrous film based on cyclodextrin (hydroxypropyl-β-cyclodextrin) inclusion complexes (ICs) incorporating a triple drug combination of acetylsalicylic acid (Aspirin), paracetamol, and caffeine (APC). The combination of these three drugs constitutes a multimodal analgesic widely used for the treatment of acute pain conditions, such as headache and migraine. Herein, the electrospun HPβCD/APC-IC nanofibrous film was fabricated with a total drug loading of ∼10 % (w/w), comprising ∼4.4/4.4/1.2 % (w/w) of each component (A/P/C), thereby matching the drug ratio found in the commercial analgesic formulation, Excedrin. 2D NMR (ROESY) analysis confirmed the IC formation between HPβCD and both acetylsalicylic acid and paracetamol. The powder form of HPβCD/APC-IC was also prepared as a control sample. XRD and DSC analyses revealed the amorphization of all three drug components within both the HPβCD/APC-IC nanofiber and powder forms. The HPβCD/APC-IC nanofibrous films exhibited significantly enhanced dissolution and disintegration performance in aqueous medium, along with improved drug release profiles, compared to their powder counterparts. HPβCD/APC-IC nanofibers demonstrate strong potential as a fast-dissolving drug delivery system, offering a promising alternative to conventional tablet dosage forms of this triple-drug combination.