Compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media.

PURPOSE: The aim of this study was to determine the compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media over a period of seven days when stored light protected under refrigerated conditions. METHODS: DC bead™ (2 ml) (Biocompatibles UK Ltd) of the bead size 70-150 µm ( = DC bead M1) or bead size 100-300 µm were loaded with 75 mg epirubicin powder formulation (Farmorubicin® dissolved in 3 ml water for injection to a concentration of 25 mg/ml) or 76 mg epirubicin injection solution (Epimedac® 2 mg/ml) within 2 h or 6 h, respectively. After removal of the excess solution, the epirubicin-loaded beads were mixed in polypropylene syringes with an equal volume (∼1.5 ml) of contrast media, i.e. Accupaque™ 300 (Nycomed Inc.), Imeron® 300 (Bracco S.p.A), Ultravist® 300 (Bayer Pharma AG), Visipaque™ 320 (GE Healthcare) and agitated in a controlled manner to get a homogenous suspension. Syringes with loaded beads in contrast media were stored protected from light under refrigeration (2-8℃). Compatibility was determined by measuring epirubicin concentrations in the suspensions in triplicate on day 0, 1, and 7. A reversed phase high-performance liquid chromatography assay with ultraviolet detection was utilized to analyze the concentration and purity of epirubicin. RESULTS: Mixing of epirubicin-loaded beads with different non-ionic contrast media released 0.1-0.5% of epirubicin over a period of 24 h, irrespectively, of the DC bead™ size or type of contrast media. No further elution or degradation was observed after seven days when the admixtures were stored protected from light under refrigeration. CONCLUSION: Compatibility of epirubicin-loaded DC bead™ with an equal volume of different contrast media in polypropylene syringes is given over a period of seven days. Due to a maximum elution of 0.1-0.5% of epirubicin from loaded DC bead™, admixtures with contrast media can be prepared in advance in centralized cytotoxic preparation units. Microbiological aspects have to be considered when determining the expiration date of the product.

Compatibility of irinotecan-loaded DC Bead with different volumes and types of non-ionic contrast media.

OBJECTIVES: Irinotecan-loaded microspheres are used for simultaneous embolisation and chemotherapy of liver metastases of colorectal carcinoma. The aim of the study was to evaluate the compatibility of recently introduced DC BeadM1 (bead size 70-150 µm) loaded with irinotecan after admixture with different types and volumes of non-ionic contrast media over a maximum period of 24 h and storage at room temperature. METHODS: Test suspensions were prepared by loading 2 mL DC BeadM1 with 100 mg irinotecan within 2 h. The loading efficiency was determined by measuring the concentrations of irinotecan in the excess solutions via a reversed phase high pressure liquid chromatography (RP-HPLC) assay with ultraviolet detection. The compatibility of irinotecan-loaded DC BeadM1 with different types and volumes of contrast media was studied by mixing 2 mL loaded bead slurry each with up to four different volumes (5, 10, 20, 30 mL) of seven different contrast media. Samples were withdrawn after 30 min, 1, 2, 4, 8 and 24 h. Admixtures were stored light protected at room temperature over the observation period. The concentrations of eluted irinotecan were measured in triplicate samples using the RP-HPLC assay. RESULTS: Mixing of irinotecan loaded beads with non-ionic contrast media decreased the irinotecan loading efficiency between minimum 2.5% and maximum 17% over the observation period of 24 h. The rate and amount of irinotecan eluted from the beads varied relying on the type and volume of contrast medium admixed. However, no further elution or degradation was observed after the rapid release during the first 8 h. CONCLUSIONS: Because of the rapid and extensive release of irinotecan, it is not recommendable to prepare admixtures of irinotecan-loaded DC BeadM1 with contrast media in centralised cytotoxic preparation units in advance. Admixture should be performed with the smallest possible amount by the radiologists immediately prior to the delivery procedure.