Direct cyclodextrin-based powder extrusion 3D printing for one-step production of the BCS class II model drug niclosamide

Abstract

Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic drug for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug and is consequently characterized by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, direct powder extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (fused deposition modelling, FDM) to achieve direct extrusion of powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-β-cyclodextrin (HP-β-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-β-CD was conducted. For all tablets, in vitro dissolution studies showed sustained drug release over 48 h, but for tablets containing HP-β-CD, the release was faster. Solid-state characterization studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets have exhibited good mechanical and physical features and a stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalized pharmaceutical forms directly from powders, avoiding the use of filament used by FDM. Graphical abstract

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

“…Although, there are several different types of 3D-printing methods, the American Society for Testing and Materials (ASTM), has categorized them into seven categories namely, (i) Vat Photopolymerization, (ii) material jetting, (iii) binder jetting, (iv) material extrusion, (v) powder bed fusion, (vi) sheet lamination, and (vii) directed energy deposition [ 102 ]. However, the most widely used technologies for the preparation of ASDs reported in the literature include direct powder extrusion [ 103 ], SLS [ 104 ], 3D inkjet printing [ 105 ], and FDM [ 106 ]. These 3D-printing technologies are capable of making ASD just by the nature of virtue of their process.…”

3D Printing Direct Powder Extrusion in the Production of Drug Delivery Systems: State of the Art and Future Perspectives

“…The extruder design is analogous to a single-screw HME, with the rotation speed controlled by the 3D printer’s software and the nozzle moving in three dimensions to allow layer-by-layer construction. This 3D printer has been used to produce drug delivery systems directly from powder blends [ 14 , 15 , 31 ].…”

“…In addition, mixtures that cannot be printed by FDM due to the inappropriate mechanical properties of the filaments obtained could be potentially extruded using this technology. In DPE, the material flow towards the printer nozzle is mainly driven by the screw rotation, which is slightly influenced by the material’s mechanical properties [ 13 , 14 , 15 , 16 ]. Moreover, the thermal stress experienced by the APIs processed by DPE is significantly reduced in comparison with FDM [ 17 , 18 , 19 ].…”

Combining 3D Printing and Microfluidic Techniques: A Powerful Synergy for Nanomedicine

“…The goal of this critical review was to focus on the potential of combining the MF technique with a three-dimensional (3D) printing technique based on this evidence. The latter technique, which has become a popular area of study applied to personalized NM [ 25 ], is one of MF’s most important allies. The combination of the two could allow the issues associated with device customization to be overcome, leading to significant advancements in subsequent production and application [ 26 ].…”