Development and analysis of a novel loading technique for FDM 3D printed systems: Microwave-assisted impregnation of gastro-retentive PVA capsular devices.

In this paper, we describe a modular post-printing loading protocol for a 3D printed gastro-retentive drug delivery system. Fused Deposition Modelling (FDM) 3D printing was exploited for the rapid prototyping of a modular floating system (caps-in-cap). Optimized models were produced as blank PVA scaffolds, and a morphological analysis of the FDM printed models was conducted to develop a straightforward protocol for drug-loading. The 3D printed gastro-retentive systems were then subjected to microwave irradiation in oversaturated solutions of anhydrous caffeine for drug loading, and research focused on an analysis of the impact of microwave irradiation on the chemical and physical properties of the polymer and the drug. The drug-loading efficiency, thermal and chemical characteristics of components, the stability of the drug and the morphology of processed printouts are characterised and described. Parameters of this unexplored microwave-assisted post-printing loading technique were evaluated and adequately set up, and the process resulted in the preservation of the polymeric matrix and enhancement of drug loading. Hence, microwave impregnation confirmed its potential in superseding the traditional pre- and post-printing loading methods, such as soaking techniques, being faster and more efficient and providing a new paradigm approach to personalised drug delivery.

Coaxial semi-solid extrusion and ionotropic alginate gelation: A successful duo for personalized floating formulations via 3D printing.

With the aim to fulfill the patient-centered approach of precision medicine, in this research, innovative floating drug delivery systems have been developed through the use of alginate matrix and fully characterized. Particularly, to exploit the ionotropic gelation of alginate, a customized coaxial extruder for Semi-solid Extrusion 3D printing, has been used for the simultaneous dispensing of ink gel (sodium alginate 6% w/v) and crosslinking gel (hydroxyethyl cellulose 3 %w/v, calcium chloride 0.1M and Tween 85 0.1% v/v). The latter also loaded with Propranolol Hydrochloride 12.5%w/v. A novel single-step process gelation for the extemporaneous gelation of loaded oral systems has been therefore developed. These technologically advanced formulations showed high printing reproducibility in manufacturing different models (mass of a single layer 535.41 ± 40.00 mg with an average drug loading efficiency of 85% w/w) and similar release behavior, paving the way for their customization in terms of drug dosages via this pioneering process.

Poly(vinyl alcohol) 3D printed tablets: The effect of polymer particle size on drug loading and process efficiency.

Fused deposition modeling by 3D-printing is a rapid technique for the production of personalized drug dosage forms. One of the most delicate step of the whole process is the drug loading onto the thermoplastic polymer to obtain the drug-loaded filament used as feedstock for 3D FDM printers. With the aim of improving the drug loading, a systematic study on the influence of polymer size distribution on the quantity of drug able to adhere onto the polymer surface was conducted. Several solid mixtures were prepared, using five PVA batches (4000-5000 µm, 1000-2000 µm, 600-1000 µm, 250-600 µm, <250 µm) and Ciprofloxacin hydrochloride as active compound in different ratios. Operative specifics and printer's parameters were tuned for an optimal print of drug-loaded filaments into the desired dosage forms, i.e. cylindrical printlets, fully characterized in terms of homogeneity, process efficiency, physical properties, drug content and release kinetics. The PVA particle size affected the polymer ability to form homogeneous mixture with the drug and the efficiency of the extrusion process. In particular, finest PVA batches showed better processability and reduced the drug loss during the drug/polymer mixing and the extrusion process. Drug-loaded filaments with different drug concentrations were successfully printed and the obtained printlets dissolution profiles were almost superimposable, taking an important step for the future application of 3D-printing manufacturing process to obtain personalized galenic formulations.