Published Research Study: "Orodispersible films prepared by hot-melt extrusion versus solvent casting"

A recent study by Mathieu Reuther, research assistant at AdhexPharma, published in the International Journal of Pharmaceutics (March 2025), compares two methods of manufacturing orodispersible films (ODF): hot melt extrusion (HME) and solvent casting (the most widely used method).

This research highlights how these techniques influence the properties of ODFs, innovative pharmaceutical forms designed for rapid dissolution in the mouth, such as Rapidfilm®, ideal for children, the elderly, and patients with conditions like dysphagia, Parkinson’s disease, among others [1].

Objective of the study:

To analyze and compare the physical and chemical characteristics of two orodispersible films with identical compositions containing a poorly soluble Active Pharmaceutical Ingredient (API) but produced via two distinct methods. The aim is to validate the application of hot melt extrusion (HME) for large-scale production by evaluating its impact on the quality, stability, and efficacy of the films.

Compared manufacturing methods:

• Solvent Casting: A widely used industrial method [2], where excipients and the API are dissolved or dispersed in a solvent (typically aqueous). The formulation is spread into a uniform layer before drying, a critical step to stabilize the film structure. While it offers formulation flexibility, it faces limitations for poorly soluble active pharmaceutical ingredients (APIs) [3].
  
  
• Hot Melt Extrusion (HME): A solvent-free, continuous manufacturing process performed in a single step [4]. This technique is gaining prominence and has already facilitated the market introduction of numerous drugs. It is particularly advantageous for poorly soluble APIs [5].

Main conclusions of the study:

• Performance: Both methods enable the production of films that comply with pharmaceutical standards in terms of disintegration and dissolution times.
  
  
• Structure: Films obtained by solvent casting exhibit a more homogeneous distribution of the plasticizer, a smoother texture, and greater flexibility. HME films can be slightly more brittle due to a less uniform integration of the plasticizer. But these criteria can be improved through optimized formulation and process parameters. However, the water absorbed by films obtained by HME does not make them more deformable, unlike those obtained by solvent casting, which gives them significantly interesting mechanical properties when stored over time.
  
  
• Stability: Both methods exhibit similar chemical stability under different humidity conditions, although recrystallization of the API may occur at high humidity levels, particularly in films prepared by solvent casting. Long-term stability tests have shown that HME films maintain their structural and chemical integrity for at least 12 months when stored in appropriate packaging.

The study confirms that the hot melt extrusion technique is an appropriate method for the industrial production of ODFs, particularly offering:

• A solvent-free process, which is more environmentally friendly
• Good stability of the final product
• Adaptability to modern pharmaceutical manufacturing

The results suggest that hot melt extrusion represents a viable and sustainable alternative to solvent casting, particularly for poorly soluble active ingredients. This study indicates that ODFs such as RapidFilms® from AdhexPharma could benefit from HME to offer even more effective solutions tailored to patients' needs.  

References: 

[1] B. Badgujar et A. Mundada, « The technologies used for developing orally disintegrating tablets: A review », Acta Pharm., vol. 61, n^o 2, p. 117‑139, juin 2011, doi: 10.2478/v10007-011-0020-8.

[2] R. P. Dixit et S. P. Puthli, « Oral strip technology: Overview and future potential », J. Controlled Release, vol. 139, n^o 2, p. 94‑107, oct. 2009, doi: 10.1016/j.jconrel.2009.06.014.

[3] A. Godbole, R. Joshi, et M. Sontakke, « Oral Thin Film Technology - Current Challenges and Future Scope », 4 mars 2018, Social Science Research Network, Rochester, NY: 3133991. https://papers.ssrn.com/abstract=3133991

[4] M. M. Crowley et al., « Pharmaceutical Applications of Hot-Melt Extrusion: Part I », Drug Dev. Ind. Pharm., vol. 33, n^o 9, p. 909‑926, janv. 2007, doi: 10.1080/03639040701498759.

[5] V. R. Kallakunta, Sarabu ,Sandeep, Bandari ,Suresh, Tiwari ,Roshan, Patil ,Hemlata, et M. A. and Repka, « An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I », Expert Opin. Drug Deliv., vol. 16, n^o 5, p. 539‑550, mai 2019, doi: 10.1080/17425247.2019.1609448.