PRINTING MUCOADHESIVE AND ORODISPERSIBLE FILMS FOR THE PERSONALIZATION OF THERAPY

Customizable oromucosal dosage forms such as orodispersible films (ODF) and mucoadhesive films (MAF) are increasingly recognized as valuable tools for addressing unmet therapeutic needs in populations requiring flexible, easy-to-administer medicines, such as paediatric and dysphagic patients. Among the proposed manufacturing techniques, extrusion-based 3D printing technologies, specifically direct powder extrusion (DPE) and semisolid extrusion (SSE) 3D printing, appear to be the most promising for the on-demand point-of-care preparation of personalized dosage forms, since they are simple processes that only require a desktop 3D printer and can potentially be carried out in a pharmacy setting. The aim of this PhD project is therefore to demonstrate the suitability of such techniques for the extemporaneous compounding of MAF (via DPE 3D printing) and ODF (via SSE 3D printing). Using DPE, MAF containing clobetasol propionate and lidocaine were obtained, achieving uniform drug loading, suitable mucoadhesive properties, controlled drug release, and favourable mucosa penetration of the loaded drug, supporting their suitability for oral inflammation and local analgesia. Then, since DPE entails exposure of the formulation components to high temperatures, hot-melt ram-extrusion (HMRE) 3D printing was tested as a milder alternative in the preparation of ODF containing the enzyme β-galactosidase, and compared with solvent casting. While HMRE resulted in the thermal degradation of the protein, enzymatic activity was completely preserved in the ODF obtained by solvent casting, which were able to digest lactose contained in milk in simulated gastric media. The attention was therefore directed toward prototyping a 3D printer that could print slurries similar to those used for solvent casting operating at room temperature, making it compatible with heat-sensitive molecules. The versatility of the resulting SSE printer was tested by preparing ODF loaded with β-galactosidase, CBD oil, and diclofenac-loaded lipid microparticles. In all cases, ODF with satisfactory properties were obtained and the payload was not negatively impacted by the process. Finally, to test the feasibility of obtaining sustained-release ODF by SSE 3D printing, a trihexyphenidyl/clay hybrid was prepared and successfully loaded into ODF, resulting in a controlled release of the drug over a 6-hour period. In conclusion, this work demonstrates the versatility of extrusion-based 3D printing technologies and their potential for the extemporaneous preparation of personalized dosage forms.