Continuous manufacturing of vitamin D3 and iron enriched granules by means of a novel twin-screw dry granulation process

Abstract

A multi-disciplinary approach involving continuous manufacturing (CM) of thermally stable food supplements containing vitamin D3 (VitD3) and iron (Fe ++ ) via a single-step twin-screw granulation (TSG) process was tested in this work. Two selected excipients, namely Neusilin® US2 and corn starch, were used in the work. The particle size distribution and morphology of pre-mixed and post-extruded granules were investigated with a laser diffraction particle size analyzer, sieve analysis, scanning electron microscopy and energy dispersive X-ray (SEM-EDX), X-ray powder diffraction (PXRD), and polarized light microscopy (PLM). The thermal stability of the granules was assessed through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The SEM visualized a good distribution of all ingredients without the forming of any crystals on the extrudate surface, indicating good mixing during the high shear granulation inside the extruder barrel. The FT-IR analysis demonstrates that characteristic vibration peaks of VitD3 were present in all physical mixtures as well as the extruded granules, indicating that VitD3 was stable in the formulations despite the high shear mixing during the TSG. The mean volumetric diameter (Dv50) of the formulation containing Neusilin increased significantly ( P < 0.05) to 90.8-μm when compared with neat Neusilin (71.3-μm) and VitD3 (33.8 μm) confirming granulation, however, no improvement was observed for the corn starch blend. In addition, the calculated Hausner ratio (HR) and Carr's index (CI) suggest similar inter-particulate friction of VitD3 and Neusilin, whereas corn starch showed a difference. The surface elemental analysis confirmed the presence of Fe ++ with a homogenous distribution of the metal in the granules. Overall, for the first time, the blend of VitD3 and iron has been prepared using the CM platform, which has great potential for the intervention of VitD3 and iron deficiencies. • Twin screw dry granulation is employed to develop vitamin D3 and iron granules. • Neusilin and corn starch are used as excipients for the blend. • Particle size distributions and morphology confirm the formation of granules. • Vitamin D3 remained almost constant in the TSG process.