title: Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt Extrusion and Film Coating.
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.
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Jedinger
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A- 8010, Graz, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Schrank
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Fischer
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Breinhälter
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria.|Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Khinast
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria. eva.roblegg@uni-graz.at.|Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A- 8010, Graz, Austria. eva.roblegg@uni-graz.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006170:Gum Arabic / Q000737:chemistry; D006358:Hot Temperature; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D004364:Pharmaceutical Preparations; D011135:Polysaccharides, Bacterial; D011208:Powders; D000431:Ethanol; C013517:ethyl cellulose; D006170:Gum Arabic; D002482:Cellulose; D013213:Starch; C002563:xanthan gum
keywords: dose dumping; drug tampering; melt extrusion; starch