3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics

Abstract

Citation: Goyanes A, Wang J, Buanz A, Martinez-Pacheco R, Telford R, Gaisford S and Basit AW (2015) 3D printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. Molecular Pharmaceutics. 12(11): 3783-4174. Key wordsThree dimensional printing; controlled-release; fused deposition modelling; PVA; paracetamol; acetaminophen; caffeine; hot melt extrusion; Raman mapping 2 AbstractThree dimensional printing (3DP) was used to engineer novel oral drug delivery devices, with specialised design configurations loaded with multiple actives, with applications in personalised medicine. A filament extruder was used to obtain drug-loaded -paracetamol (acetaminophen) or caffeine -filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3D printing. A multi-nozzle 3D printer enabled fabrication of capsule-shaped solid devices, containing paracetamol and caffeine, with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different from the drug in the adjacent layers; and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least squares component matching to produce false colour representations of distribution of the drugs showed clearly the areas that contain paracetamol and caffeine, and that there is a definitive separation between the drug layers.Drug release tests in biorelevant media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both drugs was simultaneous and independent of drug solubility. With the DuoCaplet design it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device, and the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design configurations and unique drug release characteristics, which would not otherwise be possible using conventional manufacturing methods.3

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets

“…The friability revealed no variations and was demonstrated to be 0% for all the formulation. Unlike tablets generated from other 3D printed technologies such as EXT (Khaled et al, 2014a) and powder-based 3D printing (Katstra et al, 2000b;Yu et al, 2009), the friability of tablets generated using via FDM 3D printing tends to be very low or even zero (Goyanes et al, 2014a;Goyanes et al, 2015c;Pietrzak et al, 2015).…”

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

“…There is a wide range of 3D printing technologies that operate via thermal or solvent evaporation mechanisms. FDM 3D printing is a thermal based 3D printing technique and has recently attracted the interest of researchers in many fields including pharmaceutical formulations design [1][2][3], food technology [4], and tissue engineering [5]. For pharmaceutical applications, this technique has been identified as holding future promise for developing individualized oral medicines [1][2][3][6][7][8].…”

“…FDM 3D printing can play an important role in reducing the complexity of drug regimens through incorporation of multiple drugs into a 'polypill' type of formulations. It may also allow different release profiles of the drug to be obtained through changing the exposed surface area or the geometry of the dosage form and through using more than one kind of carrier material with different drug release characteristics [7,8]. Although industrial scale FDM 3D printing is used in other sectors, until now its applications in pharmaceutical manufacturing have been limited to laboratory scale.…”

“…One of the significant constraints for the development of pharmaceutical FDM 3D printing is the extremely limited number of FDM printable materials currently available. In most reported cases, the printing of proposed oral solids were performed using mostly PVA, PLA and PCL [7][8][9]. Only recently, the uses of pharmaceutical grade polymers for FDM printing of capsules and coating layers were reported [10].…”

“…Formulations fabricated using FDM 3D printing are mostly solid dispersion based formulations [7][8][9]13]. Solid dispersions are widely used formulations for improving the dissolution of poorly water-soluble drugs [14,15].…”