(M1530-07-44) Development of Clotrimazole Oral Films via Hot-Melt Extrusion for Improved Pediatric and Geriatric Drug Delivery

Purpose: The main goal of this study was to develop and optimize hot-melt extruded (HME) oral films containing clotrimazole as a patient-friendly alternative to marketed troches/lozenges, specifically targeting pediatric and geriatric populations who face swallowing difficulties with conventional dosage forms. The study aimed to assess polymer combinations of polyethylene oxide (PEO) and hydroxypropyl cellulose (HPC) to enhance film properties such as flexibility, bioadhesion, disintegration, and drug release while avoiding the use of solvents.

Methods: Five formulations (F1–F5) of oral films containing clotrimazole (10%) were prepared using combinations of PEO and HPC with citric acid (1%) via hot-melt extrusion. Physical mixtures were prepared, sieved, and extruded at 85–95 °C using a twin-screw mini extruder. The extruded films were evaluated for physical properties, disintegration, drug content, thermal behavior, FTIR interactions, mechanical strength, bio-adhesion, and finally the in-vitro dissolution was performed in 0.1N HCl using a USP type V paddle-over-disk apparatus.

Results: Films were successfully processed at lower temperatures than the API’s melting point, with PEO-based formulations requiring lower temperatures than HPC-rich ones. The thermograms of DSC revealed a depression in the drug’s melting point in extruded films (from 147 °C to ~121 °C), indicating partial solubilization. FTIR showed no new peaks or peak disappearance, confirming compatibility. Film thickness was consistent across formulations. Tensile strength decreased with lower PEO content; F1 (high PEO) showed the highest mechanical strength, while F2 (high HPC) had the weakest. Bioadhesion was highest in F3 (equal PEO and HPC), suggesting synergistic interaction for mucoadhesion. F1 and F2 showed poor bioadhesion. The in-vitro dissolution profile of F3 released 92.3%, closely matching the marketed formulation (93.08%) with a similarity (f2) and dissimilarity factor (f1) values of 62 and 5 respectively.

Conclusion: Clotrimazole oral films were successfully developed using hot-melt extrusion, offering a solvent-free, patient-centric alternative to conventional lozenges. Among all formulations, F3 exhibited an optimal balance of mechanical properties, bioadhesion, and dissolution performance, closely mimicking the marketed product. Formulations F1 and F5 achieved complete drug release but lacked ideal adhesion or matrix behavior. This study confirms that HME-based oral films are promising platforms for improving clotrimazole delivery, particularly for populations with dysphagia. Future work should involve clinical evaluation and further optimization for scalability and stability.

References: Al-Kubati, S. S., & Okba, M. S. (2024). Formulation and evaluation of medicated lozenges containing the solid dispersion of Clotrimazole /PEG 6000 for the treatment of oral candidiasis. University of Aden Journal of Natural and Applied Sciences, 28(1), 59–71. https://doi.org/10.47372/uajnas.2024.n1.a08


Formulation Compositions (%w/w)


Dissolution profile of formulations (F1 to F5) compared with marketed formulation