Orodispersible films prepared by hot-melt extrusion versus solvent casting

Abstract

This study investigated the influence of solvent casting and hot-melt extrusion manufacturing methods on the physical, chemical, and functional properties of orodispersible films with the same composition and incorporating a poorly soluble active pharmaceutical ingredient (API). Both techniques produced films that met pharmaceutical standards for disintegration and dissolution times. Solvent casting, the most used method, yielded films with homogeneous distribution of plasticizer, smoother textures, and greater flexibility.

Highlights

• Orodispersible film manufacturing method comparison.
• Mechanical properties.
• Humidity impact.
• Pharmaceutical manufacturing requirements.

In contrast, hot melt extrusion, a solvent-free process, resulted in slightly brittle films due to uneven plasticizer integration, highlighting the impact of manufacturing parameters on film structure. Despite these differences, both methods exhibited similar chemical stability under varying humidity conditions, with API recrystallization occurring at higher humidity, particularly in films prepared by solvent casting. Increased humidity significantly reduced tensile strength, as water acted as a plasticizer, promoting API recrystallization and weakening the structure. Stability tests revealed that hot melt extrusion films retained their structural and chemical integrity over 12 months when stored in impermeable packaging bags.

This study confirms the suitability of hot melt extrusion for industrial-scale ODF production, offering advantages such as a solvent-free process, reduced environmental impact, and adaptability for modern pharmaceutical manufacturing, provided formulation and process parameters could be carefully optimized.

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Materials

The film-forming, Hypromellose (Affinisol ™ HPMC HME 15LV, CAS No. 9004-65-3), was supplied by DuPont (USA) (molecular weight < 100 kDa). The plasticizer, D–α–Tocopheryl Polyethylene Glycol Succinate (TPGS 1000, CAS No. 9002-96-4), was from PMC-Isochem (France). It’s melting point is around 38 °C (Shin and Kim, 2003). The API, belonging to the benzodiazepine class will not be detailed for confidentiality reasons (purity 99.9 %), was purchased from Cambrex (Italy). API has a melting point between 150 and 215 °C (Valenti et al., 2021) and a low water solubility (approximately 30 µg/mL) (Laihanen et al., 1996, Loftsson et al., 2001, Siegel et al., 2015). Film-forming solution was prepared using ethyl acetate (>99.8 %, CAS No. 141-78-6, VWR Chemicals, France).

Mathieu Reuther, Nicolas Rollet, Frédéric Debeaufort, Odile Chambin, Orodispersible films prepared by hot-melt extrusion versus solvent casting, International Journal of Pharmaceutics, 2025, 125536, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125536.

See also the interesting video on Vitamin E TPGS below and read more: here