Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction.

Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5 mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500 N) and very large particle size (> 1 mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5 min (% S) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30 min and % S < 15 was achieved with egglets of 6 mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation.