Lipid Complex-Itraconazole in Thermosensitive Mucoadhesive Vaginal Gel to Enhance the Effectiveness of Therapy for Vulvovaginal Candidiasis: Formulation, Optimization, Characterization, and Ex vivo Evaluation

• Published in: Journal of pharmaceutical innovation 2023-09, Vol.18 (3), p.1546-1559
• Main Authors: Sukmawaty, Muli, Sartini, Permana, Andi Dian, Mudjahid, Mukarram, Roska, Tri Puspita, Rahman, Latifah
• Format: Article
• Language: English
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Original Article; Pharmacology/Toxicology
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-023-09738-1

Purpose This study aimed to produce lipid complex-ITR (CL-ITR) to enhance the solubility of ITR which is then made into an in situ vaginal gel to maximize the local therapeutic effect of vulvovaginal candidiasis. Methods The CL-ITR was prepared by mixing ITR with Phospholipon 90G ® (P90G) in different concentrations with solvent-evaporated methods. CL-ITR optimization was carried out by determining the solubility of ITR in CL-ITR and then characterized through FTIR, DSC, SEM, and profile release of ITR. Furthermore, the optimal CL-ITR formula was mixed into the gel base using Poloxamer (PF127 and PF68) and sodium alginate (SA) as gelling agents with various concentrations. The gel characteristics were then determined through T sol-gel , pH, viscosity, time and mucoadhesive strength, and stability tests. Ex vivo evaluation was carried out using the porcine’s model to determine ITR that was permeated and retained on the vaginal mucosa and antifungal activity assay. Results The F5 with an ITR:P90G concentration of 1:5 is an optimized CL-ITR that is soluble ITR at 1275 ± 10.24 mg/mL. The G3 is the formula gel that retained the highest ITR, namely 4.72 ± 0.06 mg, and it had the lowest permeation of 1.90 ± 0.02 mg at 24 h. Furthermore, the time-killing test showed that G3 is the superlative formula against C. albicans , namely 3.58 ± 0.03 CFU/mL at 24 h. Conclusion ITR was successfully administered vaginally in the form of an in situ gel and had desirable values in every evaluation that was performed. Therefore, it can be an alternative to improve the effectiveness of ITR therapy for the treatment of vulvovaginal candidiasis.