title: Development and manufacture of diacetylmorphine/caffeine sachets for inhalation via 'chasing the dragon' by heroin addicts.
abstract: In 1998, two clinical trials were started in The Netherlands to evaluate the effect of coprescription of heroin and methadone on the mental and physical health and social functioning of chronic, treatment-resistant, heroin-dependent patients. Since 75-85% of the heroin addicts in The Netherlands use their heroin by "chasing the dragon," one of the two study arms concerned the coprescription of inhalable heroin. A pharmaceutical dosage form for inhalable heroin was developed for this trial, consisting of a 3:1 powder mixture of diacetylmorphine base and caffeine anhydrate. We describe the manufacturing process that was developed for filling sachets with this mixture in four dosages using a micro dose auger filler. In order to control product quality, in-process controls were developed to monitor the filling process and quality control tests were performed on the finished product. In-process control results have shown the filling process to be accurate and precise. The diacetylmorphine/caffeine sachets were shown to comply with the specifications for content and uniformity of mass. The finished product was found to be stable for 2 years when stored at 25 degrees C, 60% relative humidity and for 6 months when stored at 40 degrees C, 75% relative humidity.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. apmlk@slz.nl
authors.forename: M G
authors.initials: MG
authors.lastname: Klous
authors.forename: B
authors.initials: B
authors.lastname: Nuijen
authors.forename: W
authors.initials: W
authors.lastname: van den Brink
authors.forename: J M
authors.initials: JM
authors.lastname: van Ree
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000280:Administration, Inhalation; D002110:Caffeine / Q000008:administration & dosage* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D004304:Dosage Forms; D004355:Drug Stability; D003932:Heroin / Q000008:administration & dosage* / Q000627:therapeutic use; D006556:Heroin Dependence / Q000188:drug therapy; D006801:Humans; D009426:Netherlands; D011208:Powders; D011786:Quality Control; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004304:Dosage Forms; D011208:Powders; D002110:Caffeine; D003932:Heroin