Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt Extrusion and Film Coating

Abstract

Abstract. This study focused on the development of flexible (i.e., deformable) multiple-unit pellets that feature (i) a prolonged drug release, (ii) drug abuse deterrence, and (iii) a minimal risk of alcohol-induced dose dumping (ADD). Deformable pellets were prepared via an advanced continuous one-step hot-melt extrusion (HME) technique, with the drug (i.e., antipyrine and codeine phosphate) fed as an aqueous solution into the molten matrix material (i.e., cornstarch, gum arabic, and xanthan). Formulations that had suitable mechanical characteristics (i.e., high compression strength) were coated with a flexible Aquacoat ® ARC film to ensure prolonged release and to avoid ADD. The pellets were characterized in terms of their mechanical properties and in vitro drug release behavior in alcoholic media. All formulations were abuse deterrent: they had a high compression strength and grinding the pellets into powder was impossible. Since the pellets comprising gum arabic and xanthan as a matrix did not remain intact during dissolution testing, they had a very fast drug release rate. Cornstarch-based pellets that swelled but remained intact in the dissolution media had a slower drug release. Coated cornstarch-based pellets had a prolonged release over 8 h and resistance to dose dumping in 20 and 40% ethanol. Our results indicate that cornstarch-based pellets manufactured via the advanced HME process followed by coating are a promising formulation that makes tampering difficult due to a high compression strength combined with robustness in alcoholic media.

Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation

“…APAP and PEO showed endothermic melting peaks at 170.2°C (Jedinger et al, 2015) and 69.85°C (Rahman et al, 2016), respectively, due to the crystalline and semi-crystalline nature of APAP and PEO. For xanthan gum, guar gum, and gellan gum, no thermal events were recorded between 25°C and 200°C, and a broad endothermic event observed at approximately 110°C, which may have been due to evaporation of moisture content (Jedinger et al, 2016;P. More et al, 2017).…”

Dry-Coating of Powder Particles is Current Trend in Pharmaceutical Field

“…Use of meltable materials of controlled properties makes the HMC process well controllable 41 . The melt pelletization and melt granulation processes desires meltable materials having a high viscosity and a reduced particle size 42,43 . High viscosity materials are desirous to improve mechanical strength of the coating but reduced particle size desirous to prevent rough surface of coating 2,3,41 .…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part II

“…Jedinger et al [101] developed an abuse-deterrent formulation product based on HME and film coating. In this approach, first, crush-resistant pellets of codeine phosphate and antipyrine were prepared using HME.…”