title: A ceramic drug delivery vehicle for oral administration of highly potent opioids.
abstract: Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.
authors.affiliation: Division for Nanotechnology and Functional Materials, Department of Engineering Sciences, The Angström Laboratory, Uppsala University, P.O. Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Forsgren
authors.forename: Erik
authors.initials: E
authors.lastname: Jämstorp
authors.forename: Susanne
authors.initials: S
authors.lastname: Bredenberg
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.forename: Maria
authors.initials: M
authors.lastname: Strømme
mesh_terms: D000284:Administration, Oral; D000538:Aluminum Silicates / Q000737:chemistry*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077215:Clay; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005283:Fentanyl / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013499:Surface Properties
chemical_list: D000538:Aluminum Silicates; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011208:Powders; D000077215:Clay; D005283:Fentanyl