Category: Formulation and Quality
Purpose: Terconazole (TZ), an antifungal drug highly effective against ocular candidiasis without detected side effects even with intravitreal injections. Generally, topical ocular administration suffers low bioavailability due to high tear turn over, drainage through the nasolacrimal duct, transient precorneal residence time, metabolism of drug by anterior segment enzymes and presence of corneal and conjunctival barriers. TZ-loaded bile based nanovesicles (BBNV) were formulated to enhance TZ ocular residence time, permeation and reduce dosing frequency.
Methods: TZ-loaded BBNV was prepared using thin film hydration technique. Box-Behnken design was used to study the effect of different amounts of Span 60, cholesterol and sodium deoxycholate as the selected bile salt on encapsulation efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results were statistically evaluated and the different parameters were optimized to prepare a system with highest EE%, lowest PS and highest ZP. The optimized BBNV was prepared and TZ release was studied through nylon membrane. Cellular bilosomal uptake and cytotoxicity study was performed in addition to ocular tolerance study.
Results: All the prepared BBNV showed high EE% ranging from 60.0 to 86.39% with mean PS ranging from 476.9 to 999 nm and ZP higher than -33.40 mV. The optimized system showed slow TZ release profile where only 50.93 % of the encapsulated drug was released after 24 hr. The optimized system showed less cytotoxic effect and high ocular tolerability compared to drug suspension with an insignificantly different uptake.
Conclusion: The prepared TZ-loaded BBNV could be considered as a novel platform for ocular drug delivery to allow safe, effective and sustained administration of TZ, which may reduce dosing frequency and enhance corneal residence time.
Omaima El Gazayerly– Professor, Faculty of Pharmacy, Cairo University, Cairo, Al Qahirah, Egypt
Pakinam Zikry– Cairo, Al Qahirah, Egypt
Carol Yousry– Cairo, Al Qahirah, Egypt
Emad Basalious– Cairo, Al Qahirah, Egypt
Omaima El Gazayerly– Cairo University, Cairo, Cairo, Egypt