RESUMEN
OBJECTIVES: The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-solid extrusion (SSE) 3D printing. METHODS: Corn starch was used for ink preparation using ISO as model drug. The inks were characterized physicochemically and their viscoelastic properties were assessed with rheological analysis. The morphology of the printed dosage forms was visualized with scanning electron microscopy and their textural properties were evaluated using texture analysis. Dose accuracy was verified before in-vitro swelling and dissolution studies in simulated gastric fluid (SGF). KEY FINDINGS: Starch inks were printed with good resolution and high drug dose accuracy. The printed dosage forms had a soft texture to ease administration in paediatric patients and a highly porous microstructure facilitating water penetration and ISO diffusion in SGF, resulting in almost total drug release within 45 min. CONCLUSIONS: The ease of preparation and fabrication combined with the cost-effectiveness of the starting materials constitutes SSE 3D printing of starch-based soft dosage forms a viable approach for paediatric-friendly formulations in low-resource settings.
Asunto(s)
Isoniazida , Tuberculosis Latente , Niño , Formas de Dosificación , Liberación de Fármacos , Excipientes/química , Humanos , Lactante , Impresión Tridimensional , Almidón , Comprimidos/química , Tecnología Farmacéutica/métodos , AguaRESUMEN
Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (µCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.