Engineering Cocrystal-Loaded Nanofibers for Ocular Therapy: A Hybrid Electrospinning–Electrospraying Strategy

Developing solid dosage forms containing pharmaceutical cocrystals through a one-step process remains a major challenge in drug delivery. Here, we present a hybrid electrospinning-electrospraying strategy for fabricating indomethacin-saccharin (IND-SAC) cocrystal-loaded nanofibers, specifically engineered for ocular application. Poly(vinyl alcohol) (PVA) and poloxamer P407 were electrospun to form nanofiber scaffolds, followed by electrospray deposition of IND-SAC cocrystals onto the fiber surface. This dual fabrication approach aimed to enhance the drug solubility, enable <i>in situ</i> cocrystal incorporation, and achieve sustained release. The nanofibers were evaluated for rheological and mucoadhesive properties, demonstrating favorable shear thinning behavior and strong adhesion. IND-SAC cocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, Fourier-transform infrared spectroscopy, and dynamic light scattering, confirming the crystalline integrity, morphological uniformity, and absence of undesirable physicochemical interactions. <i>In vitro</i> release studies compared single-layer and bilayer nanofiber designs. Both single-layer and bilayer designs showed comparable 24 h release profiles which followed Higuchi diffusion kinetics in both systems. Mechanistic differences were observed (<i>n</i> = 0.52 vs 0.97, respectively), but these did not translate into significant differences in cumulative release. Overall, this work highlights the promise of hybrid electrospinning-electrospraying as a scalable, single-step platform for manufacturing cocrystal-loaded nanofibers. The approach combines solubility enhancement, mucoadhesion, and controlled release, addressing critical challenges in ophthalmic drug delivery and offering potential for translation into patient-friendly ocular therapies.