Ong J, Awad A, Martorana A, et al. (2020). 3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties. International Journal of Pharmaceutics. 579: 119169. doi: 10.1016/j.ijpharm.2020.119169
Researchers used 3D-printing (3DP) to fabricate alcohol-resistant, abuse-deterrent opioid tablets (printlets). Formulated from 2 grades of hydroxypropylcellulose (HPC-SL or HPC-L) and 5% tramadol, the 10g tablets printed at a rate of 45 minutes per 16-printlet batch. The printlets demonstrated strong alcohol-resistance and moderate abuse deterrence in initial tests. To improve abuse deterrence, researchers added polyethylene oxide (PEO) to the printlet formulation. HPC and PEO combined printlets (HPC-SL/PEO and HPC-L/PEO) showed significant improvements in abuse deterrence over the original HPC printlets. Syringeability tests (from 1 printlet boiled in 5 mL of water for 5 minutes) found only 13.4% (HPC-SL/PEO) and 14.7% (HPC-L/PEO) of the tramadol could be abused via intravenous injection (compared with 21.9% (HPC-SL) and 20.0% (HPC-L) of the original printlets. In tests of abuse potential via nasal inhalation (printlet milled for 2 minutes), 68.5% (HPC-SL/PEO) and 59.5% (HPC-L/PEO) of printlet particles penetrated the nasal airway (compared with 92.0% (HPC-SL) and 93.7% (HPC-L) of the original printlets). The HPC-SL/PEO and HPC-L/PEO formulations also improved the alcohol-resistance of the printlets. f2 similarity values revealed that the printlets released tramadol at similar rates in both alcoholic (40% ethanol concentration) and nonalcoholic media. f2 values between 50 and 100 indicate similarity (100 being identical). After 2 hours, f2 similarity values between tramadol released in alcoholic and nonalcoholic media were 87 (HPC-SL/PEO) and 84 (HPC-L/PEO), an improvement over the f2 similarity values of the original printlets (71 (HPC-SL) and 63 (HPC-L). Results suggest 3DP may offer an efficient new formulation approach for safer, effective opioid medications with alcohol-resistant and abuse-deterrent properties.