a School of Pharmacy and Biomedical Sciences , University of Central Lancashire , Preston , UK.
b Pharmaceutical Sciences Section, College of Pharmacy , Qatar University , Doha , Qatar.
Pharm Dev Technol. 2018 Jan;23(1):67-75. doi: 10.1080/10837450.2017.1345940. Epub 2017 Jul 19.
Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma.
Cremophor EL（CrEL）常用于增溶紫杉醇（Ptx）；Ptx 是一种广泛应用于多种癌症的抗癌药物。本研究采用基于激光的微孔比浊法，评估了 Ptx 在含有 CrEL 的制剂中，于用不同输注介质稀释或引入大鼠血浆时的沉淀动力学。评估了一种类似紫杉醇的制剂和一种 CrEL 含量降低的制剂的 Ptx 沉淀曲线。将这两种制剂以不同的比例稀释在相容的输注介质中，并分别与或不与大鼠血浆混合。采用 HPLC 定量测定稀释介质中 Ptx 的沉淀百分比和血浆中的蛋白结合率。浊度测量的结果与 HPLC 吻合良好。尽管存在白蛋白，但仍可在输注溶液中评估浊度并预测 Ptx 沉淀。加入血浆后，类似紫杉醇的制剂在 2 小时内没有发生沉淀。相比之下，CrEL 降低的制剂立即发生沉淀。可能是由于血浆中蛋白结合的 Ptx 百分比很高（98.5-99.2%），抑制了药物沉淀。激光浊度法测量可作为一种快速筛选工具，用于开发难溶性药物（如 Ptx）的静脉制剂，并在稀释至动物血浆时评估其稳定性。
