Stability of monoHER in an aqueous formulation for i.v. administration

MonoHER is a semisynthetic flavonoid used in modulating the cardiotoxic eff ect of doxorubicin but not its antitumor activity. The oral bioavailability of monoHER is < 1%. Therefore, it should be prepared as an i.v. formulatio n for use in clinical trials. The solubility of monoHER in water is highly pH dependent. At pH less than or equal to 8.3 the drug precipitates 4 h aft er preparation. DMSO was tested for enhancing the solubility of monoHER in aqueous solutions. In all DMSO-based aqueous solutions monoHER recrystalize d again at pH 8.3 and room temperature within 3 h after. preparation. Moreo ver, the stability of monoHER was lower in a DMSO stock solution than after dilution with an aqueous solution. The stability of monoHER was tested in alkaline solutions (pH 8.3 and 9.5) using an HPLC-DAD procedure to detect a ll possible degradation products within 10 min after injection. Minor degra dation occurred to monoHER in alkaline solutions when exposed to daylight o r 1% H2O2. MonoHER intensively degraded when exposed to a high temperature (80 degreesC). The stability of monoHER was almost the same in saline or 5% glucose when kept at room temperature and an alkaline pH of 8.3 and 9.5. U nder shelf-life conditions the stability of monoHER in 5% glucose (pH 8.4), decreased with about 10% during 48 h after preparation. (C) 2000 Elsevier Science B.V. All rights reserved.