Abstract:
This work aimed to formulate clotrimazole (CLZ), a water-insoluble antifungal drug, into a chitosan-coated
microemulsion system for achieving enhanced ocular delivery. In this study, CLZ loaded microemulsions were
firstly prepared according to 22 × 31 full factorial design in order to investigate the influence of different
formulation variables on microemulsion properties. The selected microemulsion formulation (F4: oleic acid,
Cremophor EL: Transcutol HP (1:1) and water (20, 70 and 10%, w/w, respectively)) showed nanosized spherical
globules with a droplet size of 229.1 ± 0.989 nm, polydispersity index of 0.5085 ± 0.0095, and zeta potential of
− 33.3 ± 0.98 mV. The selected microemulsion was then coated with low molecular weight chitosan to increase
the contact time with the eye surface. In vivo studies in albino rabbits demonstrated the superiority of chitosan-
coated microemulsion over the uncoated microemulsion and drug suspension formulation concerning sustain-
ment of antifungal activity over the eye surface. Moreover, the in vivo, ocular tolerance and histopathological
studies conducted using male albino rabbits proved the safety of the prepared microemulsions after topical
ocular application. Generally, the obtained results confirmed that CLZ chitosan-coated microemulsion could be
promising for ocular CLZ delivery.
