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

Abstract

ObjectivesIrinotecan-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.MethodsTest 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 Samples were withdrawn after 30 min, 1, 2, 4, 8 and 24 h. Admixtures were stored light protected at room temperature over the observation period.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.ResultsMixing 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.ConclusionsBecause 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.

Viability of selected microorganisms in parenteral preparations for novel systemic anti-cancer therapy

“…25 Ricci et al also mention that "protein drug product solutions have been shown to promote microbiological growth following contamination". 2 In line with our previous results, 12,13 the selected microorganisms remained viable and CFU trending in the mAb containing test solutions was mostly similar to the control solutions (see Table 2-4, Figure 2(a)). Comparable CFU growth rates were recently described for nivolumab, pembrolizumab and daratumumab.…”

“…The rather high inoculum level (10 3 -10 5 CFU/mL) was chosen according to the pharmacopoeia antimicrobial effectiveness tests and our previous experiments. 4,[11][12][13][14][15] In a recently published study the level of intended microbial contamination was also 10 5 CFU/mL. 7 Less detrimental experimental conditions are achieved, when the inoculum level is adjusted to 10² CFU/mL to simulate inadvertent touch contamination (i.e., low-level contamination).…”

“…Several studies regarding the potential of microbial growth in cytotoxic and non-cytotoxic RTA parenteral preparations have been published. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Viability tests are missing for numerous recently licensed monoclonal antibodies (mAb), filgrastim, and few small molecules introduced in anti-cancer therapy in recent years. The aim of this viability study was to investigate the potential growth promoting nature of 20 RTA parenteral preparations used for SACT.…”