Pharmaceutical development of a parenteral lyophilised formulation of the investigational anticancer agent ES-285.HCl.
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.
Den Brok
Monique W J
MW
Slotervaart Hospital/The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, 1066 EC Amsterdam, The Netherlands. apmbk@slz.nl
Nuijen
Bastiaan
B
Meijer
Dieuwke M
DM
Millán
Elena
E
Manada
Consuelo
C
Beijnen
Jos H
JH
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
D000473:Alkanes; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D005079:Excipients; D008055:Lipids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C408363:spisulosine