title: Ethanol effects on drug release from Verapamil Meltrex, an innovative melt extruded formulation.
abstract: The potential effect of ethanol to accelerate drug release from sustained release (SR) oral formulations is a general concern. Marketed Verapamil is a calcium channel blocker, mainly used as antihypertensive and anti-anginal drug and available in various dose and dosage forms. One is Verapamil Meltrex, combining an innovative and unique SR formulation and technology that achieves a stable solid dispersion of drug by using melt extrusion technology. The aim of this investigation was to determine the influence of ethanol on the in vitro rate of release of marketed Verapamil (240 mg) Meltrex, in contrast to three compressed marketed Verapamil (240 mg) SR formulations. Dissolution was tested under standardized conditions, with mediums containing ethanol concentrations of 0, 5, 20, and 40%. The dissolution profiles for Verapamil Meltrex showed no differences between 5 and 40% ethanol versus 0% ethanol (P>0.05). The mean dissolution percentage (%) was identical at 1h (19%) in 0% versus 40% ethanol. In contrast, the three comparators showed significant increases in dissolution in 20 and 40% ethanol versus 0% ethanol (P<0.001). An initial rapid release (within 2h) was observed in 20 and 40% ethanol, with a mean dissolution of 99% (range 73-107%). Therefore, unlike the three SR Verapamil formulations tested, Verapamil Meltrex was found to be resistant to in vitro dose dumping when combined with readily accessible ethanol concentrations.
authors.affiliation: SOLIQS, Abbott GmbH & Co.KG, Ludwigshafen, Germany. wolfgang.roth@abbott.com
authors.forename: W
authors.initials: W
authors.lastname: Roth
authors.forename: B
authors.initials: B
authors.lastname: Setnik
authors.forename: M
authors.initials: M
authors.lastname: Zietsch
authors.forename: A
authors.initials: A
authors.lastname: Burst
authors.forename: J
authors.initials: J
authors.lastname: Breitenbach
authors.forename: E
authors.initials: E
authors.lastname: Sellers
authors.forename: D
authors.initials: D
authors.lastname: Brennan
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D000431:Ethanol / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D013607:Tablets; D000431:Ethanol; D014700:Verapamil