A Novel Itraconazole Bioadhesive Film for Vaginal Delivery: Design, Optimization, and Physicodynamic Characterization

• Published in: AAPS PharmSciTech Vol. 10; no. 3; pp. 951 - 959
• Main Authors: Dobaria, Nitin B., Badhan, A. C., Mashru, R. C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2009
• Subjects: Adhesives; Administration, Intravaginal; Algorithms; Antifungal Agents - administration & dosage; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning; Cell Survival - drug effects; Chemistry, Pharmaceutical; Drug Design; Excipients; HeLa Cells; Humans; Humidity; Itraconazole - administration & dosage; Itraconazole - chemistry; Itraconazole - pharmacokinetics; Lactobacillus; Lactobacillus - drug effects; Particle Size; Pharmacology/Toxicology; Pharmacy; Research Article; Tensile Strength; bioadhesive films; factorial design; vaginal drug delivery; physicochemical properties
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-009-9288-0

The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. Itraconazole was formulated in bioadhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. In addition, percentage drug retained on vaginal mucosa was evaluated using a simulated dynamic vaginal system as function of time. A polymeric film containing 100 mg itraconazole per unit (2.5 cm × 2.5 cm) have been developed using generally regarded as safe listed excipients. The pH of vaginal film was found to be slightly acidic (4.90 ± 0.04) in simulated vaginal fluid and alkaline (7.04 ± 0.07) in water. The little moisture content (7.66 ± 0.51% w / w ) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break (9.64 N/mm 2 and 67.56% for ITRF 65 ) reveal that the formulations were found to be soft and tough. The films (ITRF 65 ) contained solid dispersion of itraconazole (2.5)/hydroxypropyl cellulose (1)/polyethylene glycol 400 (0.5), which was found to be the optimal composition for a novel bioadhe s ive vaginal formulation, as they showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. Also, the film did not markedly affect normal vaginal flora (lactobacillus) and was noncytotoxic as indicated by the negligible decrease in cell viability.