title: Pharmaceutical development of a parenteral lyophilised formulation of the investigational anticancer agent ES-285.HCl.
abstract: The aim of this study was to design stable parenteral pharmaceutical final products containing 25 mg and 50 mg ES-285.HCl per dosage unit for use in phase I clinical trials. ES-285.HCl drug substance was fully characterised and showed very slight solubility in water. The development of the pharmaceutical product, containing 2-hydroxypropyl-beta-cyclodextrin, is discussed in view of formulation optimisation and manufacture. The developed freeze-dried products were found stable for at least 6 months at an accelerated storage condition of 25 +/- 2 degrees C/60 +/- 5% relative humidity and for at least 12 months at the designated long term storage condition of 5 +/- 3 degrees C, in the dark. Phase I trials using ES-285.HCl 25 mg/vial and 50 mg/vial final products are currently ongoing.
authors.affiliation: Slotervaart Hospital/The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, 1066 EC Amsterdam, The Netherlands. apmbk@slz.nl
authors.forename: Monique W J
authors.initials: MW
authors.lastname: Den Brok
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
authors.forename: Dieuwke M
authors.initials: DM
authors.lastname: Meijer
authors.forename: Elena
authors.initials: E
authors.lastname: Millán
authors.forename: Consuelo
authors.initials: C
authors.lastname: Manada
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000473:Alkanes / Q000737:chemistry / Q000592:standards*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000592:standards*; D004339:Drug Compounding; D004340:Drug Contamination; D004355:Drug Stability; D004356:Drug Storage; D015507:Drugs, Investigational / Q000737:chemistry / Q000592:standards*; D005079:Excipients / Q000737:chemistry; D008055:Lipids / Q000737:chemistry / Q000592:standards*; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000473:Alkanes; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D005079:Excipients; D008055:Lipids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C408363:spisulosine