Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity

Abstract

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an AL type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

An Overview on Cyclodextrin and Its Derivatives Encapsulated Inclusion Complex: Preparation Methods and Influencing Factors

“…Spray drying with sealed heating techniques of preparation resulted in improved complex formation in the case of α-CD, β-CD, and γ-CD, and kneading is found to be ineffectual, as stated by scientists who have examined the effect of α-CD, β-CD, and γ-CD on Ibuproxam. Chowdary and colleagues investigated the interaction of Nimesulide with β-CD and found that the kneading method resulted in more drug dissolution than coevaporation [26]. Palmieri et al found that for β -CD, HP β -CD, and Methoxybutyrate, the best complexation results were obtained via solid dispersion, kneading was unsuccessful, while spray-drying resulting in complete complexation with a fixed ratio of 1:4 [29].…”

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis

“…15 The antimycotic activity showed substantial enhancement of FNL with FNL inclusion complex (FNL-IC) against Candida albicans and Candida glabratan strains. 16 Traditional ocular drug delivery systems used include topical formulations such as eye drops (solutions, suspensions, and emulsions), gels, ointments, and injections (including subconjunctival and intrascleral injections). 17 However, limitations associated with the topical application include drug washout through the nasolacrimal duct resulting in 80% of the drug not reaching the target, dilution in the tear fluid, drug metabolism, and drainage into the systemic circulation.…”

“…Previous studies have shown that IC of FNL with SB-β-CD and hydroxypropyl-β-cyclodextrin can increase the bioavailability of the drug . The antimycotic activity showed substantial enhancement of FNL with FNL inclusion complex (FNL-IC) against Candida albicans and Candida glabratan strains …”