Doxorubicin-loaded drug-eluting beads (DC Bead®) for use in transarterial chemoembolization: A stability assessment

Abstract

Purpose: Evaluation of doxorubicin stability over time when stored into the DC Bead embolic agent, in various containers, which are used for the delivery of the doxorubicin-loaded beads to the patients for up to 14 days under refrigerated conditions. Methods: The doxorubicin was loaded through the ionic exchange mechanism into the calibrated polyvinyl alcohol-based hydrogel beads (DC Bead), with the loading process carried out either in the original DC Bead glass vials or within a polypropylene plastic syringe. The loaded samples were eluted at given time points and the extracted doxorubicin was analysed by high-performance liquid chromatography for concentration and chromatographic area response purity. Results: The variance on the doxorubicin concentration of the samples stored in the syringes under refrigerated conditions was less than 10% over the 14 days period. The chromatographic purity of doxorubicin eluted from the DC Bead in their primary glass vial packaging was measured at 99.7%. The dissolution test showed that the elution rate and amount recovered from samples stored in vials were statistically similar between Day 0 and Day 14. The chromatographic purity of the doxorubicin loaded into DC Bead in presence of non-ionic contrast medium was >99.0% for 7 days under refrigerated conditions. Conclusions: Doxorubicin-loaded DC Bead® are shown to have adequate physicochemical stability over a period of 14 days when stored in syringes or vials under refrigerated conditions for up to 14 days. The admixtures of doxorubicin-loaded beads with contrast medium are stable for up to 7 days under refrigerated conditions.

Systematic review comparing the safety and efficacy of conventional and drug‐eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma

“…The mobility of the lipiodol leads to damage of the surrounding liver tissue, and is more likely to have ectopia embolization . However, the beads used in DEB‐TACE are solid, which could be able to be located more accurately and slowly release doxorubicin . Microspheres (50–100 μm in dry form in van Malenstein et al .…”

“…52,53 However, the beads used in DEB-TACE are solid, which could be able to be located more accurately and slowly release doxorubicin. 54 55,56 Our systematic review has several limitations. First, some of the included trials had small sample sizes, which can lead to selection bias.…”

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

“…During the compatibility studies, the bead size (70–150 µm) and the type and amount of drug-loaded (irinotecan, 100 mg/2 mL beads) remained unchanged whereas the type and volume of contrast media varied. These parameters were chosen because small bead sizes are preferably used nowadays, and irinotecan is known to be more rapidly eluted after admixture with contrast media than doxorubicin 9 11. Various types and volumes of contrast media were tested with regard to clinical practice.…”

Review of the Development of Methods for Characterization of Microspheres for Use in Embolotherapy: Translating Bench to Cathlab

“…The ability of the physician to consistently administer the suspension will also be a significant factor in evaluating the performance of the composition. The chemical properties of contrast agents can also influence the chemical stability and elution properties of drug‐loaded microspheres and any ionic interaction must be carefully analyzed prior to use . For example, contrast agents with high ionic contents such as Visipaque (GE Healthcare) have been shown to be associated with rapid elution of some ionically bound drugs .…”

“…For example, contrast agents with high ionic contents such as Visipaque (GE Healthcare) have been shown to be associated with rapid elution of some ionically bound drugs . Chemical stability and chromatographic purity are determined from high‐performance liquid chromatography (HPLC) testing of drug compounds, this can then be used to issue recommendations regarding the storage and use of drug‐loaded microsphere suspensions …”