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 in situ 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. In vitro 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 (n = 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.