title: The design of controlled-release formulations resistant to alcohol-induced dose dumping--a review.
abstract: The concomitant intake of alcoholic beverages together with oral controlled-release opioid formulations poses a serious safety concern since alcohol has the potential to alter the release rate controlling mechanism of the dosage form which may result in an uncontrolled and immediate drug release. This effect, known as alcohol-induced dose dumping, has drawn attention of the regulatory authorities. Thus, the Food and Drug Administration (FDA) recommends that in vitro drug release studies of controlled-release dosage forms containing drugs with narrow therapeutic range should be conducted in ethanolic media up to 40%. So far, only a limited number of robust dosage forms that withstand the impact of alcohol are available and the development of such dosage forms is still a challenge. This review deals with the physico-chemical key factors which have to be considered for the preparation of alcohol-resistant controlling dosage forms. Furthermore, appropriate matrix systems and promising technological strategies, which are suitable to prevent alcohol-induced dose dumping, are discussed.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Jedinger
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Khinast
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens University, Graz, Austria. Electronic address: eva.roblegg@uni-graz.at.
authors.forename: E
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D000284:Administration, Oral; D000428:Alcohol Drinking / Q000009:adverse effects*; D000434:Alcoholic Beverages / Q000009:adverse effects*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D000431:Ethanol / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D000431:Ethanol
keywords: Alcohol; Controlled-release; Dose dumping; Hot-melt extrusion; Hydrophilic matrices; Physico-chemical factors