3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

Abstract

In the past decade, prescriptions for opioid medicines have been exponentially increasing, instigating opioid abuse as a global health crisis associated with high morbidity and mortality. In particular, diversion from the intended mode of opioid administration, such as injecting and snorting the opioid, is a major problem that contributes to this epidemic. In light of this, novel formulation strategies are needed to support efforts in reducing the prevalence and risks of opioid abuse. Here, modified release tramadol printlets (3D printed tablets) with alcohol-resistant and abuse-deterrent properties were prepared by direct powder extrusion three-dimensional printing. The printlets were fabricated using two grades of hydroxypropylcellulose (HPC). Both formulations displayed strong alcohol-resistance and had moderate abuse-deterrent properties. Polyethylene oxide (PEO) was subsequently added into the formulations, which improved the printlets' resistance to physical tampering in nasal inhalation tests and delayed their dissolution in solvent extraction tests. Overall, this article reports for the first time the use of direct powder extrusion three-dimensional printing to prepare drug products with both alcohol-resistant and abuse-deterrent properties. These results offer a novel approach for the safe and effective use of opioids that can be combined with the advantages that 3D printing provides in terms of on-demand dose personalisation.

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

“…In the pharmaceutical field, 3D printing offers the opportunity to make a significant technological contribution in the design and manufacture of medicines [17] . When compared to conventional manufacturing processes, this technology offers unique benefits for the manufacture of solid drug products, such as patient-tailored medicines [18] , retentive devices [19 , 20] , and customised drug release formulations [21 , 22] . Within the pharmaceutical field five main 3DP technologies are currently used; powder bed ink jet printing [23] , fused deposition modelling (FDM) [24] , selective laser sintering (SLS) [25] , stereolithography (SLA) [26] , and semi-solid extrusion (SSE) [27 , 28] .…”

Polyvinyl Alcohol-Based 3D Printed Tablets: Novel Insight into the Influence of Polymer Particle Size on Filament Preparation and Drug Release Performance

“…In addition, HME provides the opportunity to surpass the solubility issues of poorly soluble APIs through solid dispersion preparation, a system wherein the drug is molecularly disseminated into the carrier matrix [ 11 ]. However, according to recently published investigations, similar advantages could be obtained by employing a newly reported printing technique, namely direct powder extrusion 3D printing, which is a single-phase preparation method that eliminates the HME phase [ 12 , 13 , 14 ].…”

Production of Drug Delivery Systems Using Fused Filament Fabrication: A Systematic Review

“…Thus, another trend was introduced by a few research groups in which the raw materials were directly fed into the printer. Recently, research groups such as Fanous et al [ 75 ], Ong et al [ 76 ], and Goyanes et al [ 77 ] discussed this approach. However, it is critical to understand that raw material homogeneity is the most important factor in this process.…”

“…Fanous et al [ 75 ] used a piston extruder in the 3D printing process that does not offer any mixing abilities during printing. On the other hand, Ong et al [ 76 ] and Goyanes et al [ 77 ] used a single screw extruder that has minimal capacity for mixing and homogenizing. Moreover, Justino Netto and Silveira [ 78 ] illustrated a prototype of a 3D printer fitted with a double screw extruder.…”