Sarakbi Iman, Krämer Irene
Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Langenbeckstraße, Mainz, Germany.
Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Langenbeckstraße, Mainz, Germany
J Oncol Pharm Pract. 2016 Dec;22(6):749-756. doi: 10.1177/1078155215607088. Epub 2015 Oct 1.
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.
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.
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.
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.
本研究的目的是确定在冷藏条件下避光储存7天期间，载有表柔比星的DC bead™与不同非离子型造影剂的相容性。
将粒径为70 - 150 µm的DC bead™（2 ml）（英国生物相容性公司）或粒径为100 - 300 µm的DC bead™分别在2小时或6小时内装载75 mg表柔比星粉剂（将法玛新®溶解于3 ml注射用水中配制成浓度为25 mg/ml）或76 mg表柔比星注射液（表柔比星®2 mg/ml）。去除多余溶液后，将载有表柔比星的微球在聚丙烯注射器中与等体积（约1.5 ml）的造影剂混合，即碘克沙醇™300（奈科明公司）、碘美普尔®300（博莱科公司）、优维显®300（拜耳医药保健公司）、威视派克™320（通用电气医疗集团），并以可控方式搅拌以获得均匀悬浮液。装有微球与造影剂混合物的注射器在冷藏（2 - 8℃）且避光条件下储存。通过在第0天、第1天和第7天对悬浮液中的表柔比星浓度进行一式三份测量来确定相容性。采用带紫外检测的反相高效液相色谱法分析表柔比星的浓度和纯度。
载有表柔比星的微球与不同非离子型造影剂混合，在24小时内释放0.1 - 0.5%的表柔比星，与DC bead™的粒径或造影剂类型无关。当混合物在冷藏且避光条件下储存7天后，未观察到进一步的洗脱或降解。
载有表柔比星的DC bead™与聚丙烯注射器中等体积的不同造影剂在7天内具有相容性。由于载有表柔比星的DC bead™中表柔比星的最大洗脱量为0.1 - 0.5%，可在集中细胞毒性制剂制备单元中提前制备与造影剂的混合物。在确定产品有效期时必须考虑微生物学方面的因素。
