ABSTRACT Voriconazole, a broad‐spectrum triazole antifungal, is widely prescribed for fungal keratitis (FK) caused by Candida , Aspergillus , and Fusarium species. Conventional ophthalmic solutions are limited by rapid clearance and low bioavailability. This study describes the development of a voriconazole‐loaded ophthalmic emulsion to improve ocular residence and drug disposition. Emulsions were prepared with soybean oil and Tween 80 via high‐shear homogenization, with batch VE‐3 exhibiting favorable properties, including nanosized globules (95.8 ± 50.2 nm, PDI 0.197), pH 6.94 ± 0.14, high drug content (104.55% ± 7.9%), and physicochemical stability. DSC confirmed the absence of drug–excipient interactions, whereas osmolality (280 ± 4 mOsm/L) and conductance (77.59 ± 1.7 S/m) demonstrated ocular compatibility. To enhance mucoadhesion and prolong corneal residence, chitosan was incorporated into VE‐3, yielding CS‐VE‐3. In vitro release studies showed 81% drug release from VE‐3 versus 65% from CS‐VE‐3, with the latter following Higuchi kinetics, consistent with sustained release. Ex vivo transcorneal studies revealed comparable permeation for VE‐3 (43.2% ± 1.14%) and CS‐VE‐3 (47% ± 1.22%), but distinct drug retention profiles (11.41% ± 0.73% vs. 5.09% ± 0.30%). In vivo pharmacokinetic assessment demonstrated C max values of 9.66 ± 3.49 μg/mL (marketed), 10.47 ± 6.43 μg/mL (VE‐3), and a four‐folds higher 41.67 ± 28.48 μg/mL for CS‐VE‐3, indicating prolonged corneal contact with chitosan incorporation. Ocular irritation studies confirmed safety and tolerability. The optimized mucoadhesive emulsion offers a promising strategy for sustained ocular delivery of voriconazole, potentially improving therapeutic outcomes in FK management.
Bisen et al. (Sat,) studied this question.