Hp--CD-VoriconazoleIn SituGelling System for Ocular Drug Delivery:In Vitro, Stability, and Antifungal Activities Assessment

Abstract

The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP-β-CD Voriconazole (VCZ) in situ gelling formulations. The in situ gelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (T gel), in vitro permeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches of in situ formulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in T gel with increase in viscosity and mucoadhesive strength. The in vitro drug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation against Candida albicans and Asperigillus fumigatus confirmed that designed formulation has prolonged effect and retained its properties against fungal infection.

Voriconazole Composited Polyvinyl Alcohol/Hydroxypropyl-β-Cyclodextrin Nanofibers for Ophthalmic Delivery

“…Therefore, in this study we developed nanofibers which formed three-dimensional networks with the ability to swell in aqueous solvents in a controlled manner [18], with the aim to achieve higher bioavailability and controlled ocular delivery. As an effective antifungal concentration [11, 12], we set the dose at 60 μg for the pharmacokinetics study. The established HPLC method for VRC determination met the in vivo analytical requirements.…”

“…Topical VRC can penetrate the cornea, and therapeutic concentration can be achieved in the cornea, aqueous humor and vitreous body [8, 9]. To date, no topical formulation for ocular use has become commercially available, although several attempts involving cyclodextrin based eye drop solutions and gels [10, 11], microemulsions [12], liposomes [13], and niosomes [14] have revealed the potential of VRC for topical ophthalmic administration.…”

“…To the best of our knowledge, electrospun nanofibers for ophthalmic applications have not been previously investigated. In the present study, HPβCD was used in the formulation to solubilize VRC [11]. The application of cyclodextrins in ocular inserts has been reported previously [22].…”

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

“…In the case of ocular in situ-forming gels sol-gel transition must be induced by ocular surface conditions such as surface eye temperature [3], tear pH [4] or ionic environment changes [5]. Ion-activated in situ gelling systems have great potential as ocular drug delivery systems due to the presence of mono and divalent cations such as Na + , K + , Mg 2+ and Ca 2+ in eye tear.…”

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“…The optimized formulation was stored in tightly closed amber glass vials (shielded from light)in the humidity chamber and the clarity, pH and drug content periodically assessed (0, 3 weeks, 6 weeks, 6, 9 and 12 months). The experiments were done in triplicate 36,37 .…”