Hot-melt Ram extrusion 3D printing: a versatile method for tailor-made orodispersible films

Orodispersible films (ODF) are a promising alternative to conventional oral dosage forms to therapy personalization and the improvement of patient adherence [1]. Recently, hot-melt ram-extrusion 3D printing (HRP) has been proposed to obtain ODF of different strengths and geometries [2]. In particular, this technology permitted to obtain individually printed ODF in three simple steps starting from a solvent-free mixture. First, solid components of formulation (e.g., drug, maltodextrin, colourants, flavours, sweeteners) are mixed in a mortar and wetted with the plasticizer (i.e. glycerine). The mixture is fed into the chamber of the ramextruder and heated up to 90°C. Then, melt material is extruded through a 0.8-mm nozzle and ODF are printed directly on the packaging material foil. To demonstrate the versatility of the technology, three different model drug substances were loaded in printed ODF. The paracetamol (PAR) was used to assess the drug loading capacity of the ODF; the diclofenac sodium (DNa), a thermosensitive drug, and olanzapine (OLZ), a polymorphic drug, were used to determine how preparation steps (e.g., heating, water-free) impacted on the drug physicochemical stability. All printed ODF were also tested in terms of assay, tensile and dissolution patterns. ODF prepared by casting were used as controls. The prepared ODF (6 cm2; thickness 150-250 μm) disintegrated in less than 1 min and showed acceptable tensile properties to be handled. Residual water contents were in the 6-8% w/w range. PAR was loaded up to 37.5% w/w in the ODF matrix without altering the film performances. The heating step induced a slight degradation of DNa in ODF, but the impurity threshold was lower than Ph. Eur. limits. Both PAR and DNa dissolution profile of printed ODF (t80 < 6min) overlapped with those of casting ODF. On the contrary, printed ODF released about 90% of OLZ was released in ~3 min, while a yellow precipitate was observed in casting ODF, suggesting a change in the OLZ solid state. This work demonstrated that HRP was a versatile technology to prepare ODF loaded with drugs with different physicochemical properties.