Development of 3D printed controlled drug delivery systems by dual Fused Deposition Modelling (FDM): Role of formulation and internal geometry on modulation of drug release

• Autores: Fatemeh Shojaie
• Directores de la Tesis: Isidoro Caraballo Rodríguez (dir. tes.), Carmen Ferrero Rodríguez (dir. tes.)
• Lectura: En la Universidad de Sevilla ( España ) en 2025
• Idioma: inglés
• Número de páginas: 136
• Enlaces
  • Tesis en acceso abierto en: Idus
• Resumen

  • Three-dimensional (3D) printing is an innovative manufacturing technology with great potential for manufacturing customizable pharmaceutical dosage forms. Its advantages include the ability to adjust the drug dose, combine multiple drugs, create versatile geometric shapes, and modulate drug release. Fused Deposition Modelling (FDM), a thermal extrusion-based technique, is the most used 3D printing technique due to its simplicity and low cost. Dual-nozzle FDM allows the extrusion of two different polymeric filaments simultaneously to produce Drug Delivery Systems (DDS) with sophisticated geometries, precise API distribution and customized drug release kinetics.

    The aim of this Ph.D. Thesis is to develop 3D printed controlled DDS using the dual-nozzle FDM technique and to evaluate the effect of the formulation and the internal geometry of the system on the drug release behavior.

    Bicompartmental DDS intended for colon-specific delivery of the model drug 5-aminosalicylic acid (5-ASA) are introduced in Chapter I. Based on two model designs (Models 1 and 2), different formulations and geometries were chosen for each compartment. Regarding the formulation, hydroxypropyl methylcellulose acetate succinate (HPMCAS, HG and HMP grades) and polyvinyl alcohol (Parteck® MXP PVA) were selected as the matrix-forming polymers of the pH-dependent outer compartment and the water-soluble inner compartment, respectively. Drug-free HPMCAS and drug-loaded (20% w/w) Parteck® MXP filaments were successfully extruded using single screw extrusion. Their physicochemical and mechanical properties were then assessed by thermal analysis, X-ray diffraction, microscopy, and texture analysis techniques to demonstrate their suitability as 3D printing feedstock materials. Thermal analysis showed that both filaments were stable at extrusion and printing temperatures, remaining 5-ASA mostly crystalline in the PVA filament. The filaments also exhibited adequate surface morphology and mechanical properties. Bicompartmental devices were successfully printed from the made-in-house filaments using two different designs. Model 1 combined an outer compartment with cylindrical geometry and an inner compartment with a spiral shape that communicated with the external media through an opening at the top of the device. The outer compartment of Model 2 was printed with a lower infill density (50% vs 100%) and a fully sealed top surface. In vitro drug release studies demonstrated that the bicompartmental DDS showed biphasic drug release profiles: sustained release at pH?1.2 and 6.8 and fast release at pH?7.4. Drug release kinetics were controlled by polymer solubility, the intricate geometry of the inner compartment, and the infill density of the outer compartment. In Chapter II, innovative core-shell DDS were developed to provide sustained delivery of 5-ASA in the intestinal region. Made-in-house drug-loaded (10% w/w) filaments were successfully extruded from the pH-dependent Eudragit®?S100 and the water-soluble Parteck®?MXP PVA polymers. These filaments also showed suitable physicochemical and mechanical properties for 3D printing. Cylindrical core-shell devices combining a water-soluble inner core and a pH-dependent, channeled outer shell were successfully obtained from the drug-loaded Parteck® and Eudragit® filaments, respectively. In vitro drug release tests demonstrated that the core-shell DDS exhibited a sustained drug release profile with different drug release rates at each pH range. Drug release kinetics were controlled by the size of the openings present in the shell and the spatial distribution of the drug.

    Overall, the research in this Ph.D. Thesis demonstrates the feasibility of the dual-nozzle FDM 3D printing technique to manufacture versatile DDS in which drug release kinetics can be modulated by modifying the formulation and the system’s architectural structure. Consequently, drugs can be released at specific rates and sites within the gastrointestinal tract.