Pfizer, Biotherapeutics/Pharmaceutical R&D - BioTherapeutics Pharmaceutical Sciences, Chesterfield, Missouri 63017.
Pfizer, Biotherapeutics/Pharmaceutical R&D - BioTherapeutics Pharmaceutical Sciences, Chesterfield, Missouri 63017.
J Pharm Sci. 2019 Jul;108(7):2406-2414. doi: 10.1016/j.xphs.2019.02.020. Epub 2019 Mar 5.
Particulate matter present in drug products intended for parenteral administration to patients is typically monitored and controlled in the finished drug product to minimize potential risks to patients. In contrast to particulates found in drug products, the current study evaluated particulates representative of materials and operations typically used in the dose preparation and administration of drug products. A comprehensive assessment of intrinsic and extrinsic sources of subvisible and submicron particulates arising from materials associated with subcutaneous and intravenous dose preparation and administration was conducted. In particular, particles arising from disposable syringes, commercial sterile diluents, and intravenous supplies were quantitated using established methods for subvisible (light obscuration, flow imaging) and submicron particles (resistive pulse sensing). Each of these sources contributed varying amounts of particulates; therefore, owing to sources from materials required for administration, it is inadequate to assume that the total particulate load delivered to patients arises solely from the drug product. Careful consideration of the administration method and supplies used can improve the predictability of particulate levels present in dose preparations or administration volumes.
用于向患者进行肠胃外给药的药物产品中存在的颗粒物质通常在药物产品中进行监测和控制，以最大限度地降低对患者的潜在风险。与药物产品中发现的颗粒物质不同，本研究评估了药物产品的剂量准备和给药过程中通常使用的材料和操作所代表的颗粒物质。对源自与皮下和静脉内剂量准备和给药相关的材料的固有和外在亚可见和亚微米颗粒的来源进行了全面评估。特别地，使用用于亚可见颗粒（光遮挡，流动成像）和亚微米颗粒（电阻脉冲感应）的既定方法对来自一次性注射器、商业无菌稀释剂和静脉内用品的颗粒进行了定量。这些来源中的每一个都产生了不同数量的颗粒物质；因此，由于给药所需的材料的来源，不能假设输送给患者的总颗粒负荷仅来自药物产品。仔细考虑给药方法和所用的供应品可以提高剂量制剂或给药体积中存在的颗粒水平的可预测性。
