The Effect of the New Imidazole Derivatives Complexation with Betacyclodextrin, on the Antifungal Activity in Oropharyngeal Infections

Abstract

Ketoconazole (KZ) is a broad-spectrum drug used to treat fungal infections. Local use of ketoconazole has been associated with some side effects in healthy adults, especially local reactions, such as stinging, severe irritation, and itching. Moreover, the bioavailability of KZ after oral administration is low in tablets due to its low water solubility. In addition, oral administration of ketoconazole produces systemic exposure, associated with significant side effects, such as cholestatic and hepatocellular lesions. In an attempt to reduce hepatotoxicity, ketoconazole may be administered at the primary site of infection with cutaneous candidiasis, specifically on the skin tissue. However, the use of ketoconazole in topical dosage forms is limited by its high lipophilicity and extremely poor aqueous solubility (1 ng/mL), thus leading to the rare availability of topical dosage forms on the market. Therefore, a new approach to the effective delivery of ketoconazole to the site of infection is targeted, including obtaining new derivatives (keeping the imidazolic nucleus), with a similar spectrum of action, and finally, their inclusion in betacyclodextrin complexes in order to optimize bioavailability and physico-chemical stability.