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

MonoHER is a semisynthetic flavonoid used in modulating the cardiotoxic effect of doxorubicin but not its antitumor activity. The oral bioavailability of monoHER is <1%. Therefore, it should be prepared as an i.v. formulation 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 after preparation. DMSO was tested for enhancing the solubility of monoHER in aqueous solutions. In all DMSO-based aqueous solutions monoHER recrystalized again at pH 8.3 and room temperature within 3 h after. preparation. Moreover, 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 all possible degradation products within 10 min after injection. Minor degradation occurred to monoHER in alkaline solutions when exposed to daylight or 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. Under shelf-life conditions the stability of monoHER in 5% glucose (pH 8.4), decreased with about 10% during 48 h after preparation.