Chitosan And Carboxymethylchitosan Mucoadhesive Oral Film Forming Spray For Local Delivery Of Fluconazole For Treatment Of Oral Candidiasis

Abstract

This study aims to develop an efficient local oral mucoadhesive film-forming spray for the targeted delivery of fluconazole, intended for the treatment of oral candidiasis. Chitosan and its water-soluble derivative, carboxymethylchitosan, were employed as key polymers in the formulation. While chitosan was solubilized in 0.5% acetic acid aqueous solutions due to its insolubility in water, carboxymethylchitosan was readily soluble in water. Notably, chitosan formulations, characterized by an acetic aroma and low pH, were primarily included for comparative purposes, acknowledging their potential for oral mucosal irritation.

Ten formulations, denoted as C14-C24, were meticulously prepared for this investigation. Utilizing a quadratic user-defined mathematical optimization model within Design-Expert 13, the optimal concentrations of carboxymethylchitosan and PEG 400 for maximal mucoadhesion were determined. The resultant formulation, comprising 20.03% PEG and 1.5% CMCH, exhibited a high desirability score of 0.989 in the Design-Expert 13 analysis. This composition closely resembled formulation C18, consequently identified as the selected formulation due to its superior mucoadhesive properties and rapid drying time.

Subsequent analyses, including ex vivo permeation studies, in vivo irritation assessments, in vitro anti-candida effectiveness, and stability evaluations, were conducted on formulation C18. It can be concluded from the comprehensive findings from these advanced analyses collectively affirmed the optimal pharmaceutical attributes of formulation C18, underscoring its potential as a promising candidate for effective oral candidiasis treatment as spray forming film drug delivery system.