Formulation, Characterization and Hypersensitivity Evaluation of an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex
Formulation, Characterization and Hypersensitivity Evaluation of an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex
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DOI：
10.1248/cpb.59.321
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发表时间：
2011-03-01
影响因子：
1.7
通讯作者：
Wang, Ren-Yun
中科院分区：
文献类型：
--
作者：
Xia, Xue-Jun;Guo, Rui-Fang;Wang, Ren-Yun
本文的目的是开发一种新型的不含 Cremophor、高压灭菌稳定的紫杉醇静脉注射乳剂 (PACE)。采用紫杉醇胆固醇复合物作为药物载体，提高紫杉醇在乳剂油相中的溶解度。复合物和PACE分别通过旋转蒸发和高压均质制备。研究了油相、乳化剂和pH值对PACE特性的影响。 PACE 的外观、形态、重量克分子渗透压浓度、坑值、粒径、zeta 电位、包封效率和稳定性进行了表征。通过豚鼠过敏反应评价过敏情况。最终配方由复合物、大豆油、中链甘油三酯、大豆卵磷脂、泊洛沙姆188和甘油组成。所得PACE的包封率为97.3%，粒径为135 nm，zeta电位为-38.3 mV。制剂的渗透压和pH值分别为-38.3 mOsmol/kg和4.5。该制剂在115℃高压灭菌30分钟后仍可存活，并在6℃下保持稳定至少12个月。PACE在豚鼠体内也表现出比等剂量基于Cremophor的紫杉醇注射液更好的耐受性，没有观察到明显的过敏反应。这些结果表明PACE具有工业规模生产和临床应用的巨大潜力。
The objective of this paper was to develop a novel Cremophor-free, autoclave stable, intravenous emulsion for paclitaxel (PACE). A paclitaxel cholesterol complex was used as the drug carrier to improve the solubility of paclitaxel in the oil phase of emulsions. The complex and PACE were prepared by rotary evaporation and high-pressure homogenization, respectively. Effects of oil phases, emulsifiers and pH values on the characteristics of PACE were investigated. PACE was characterized with regard to its appearance, morphology, osmolality, pit value, particle size, zeta potential, encapsulation efficiency and stability. Hypersensitivity was evaluated by guinea pig hypersensitivity reaction. The final formulation was composed of the complex, soybean oil, medium-chain triglyceridel, soybean lecithin, poloxamer 188 and glycerol. The resulting PACE had an encapsulation efficiency of 97.3% with a particle size of 135 nm and a zeta potential of -38.3 mV. Osmolality and pH of the formulation were -38.3 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115 degrees C for 30 min and remained stabile for at least 12 months at 6 degrees C. PACE also exhibited a better tolerance than an equal dose of Cremophor-based paclitaxel injection in guinea pigs, as no obvious hypersensitivity reaction was observed. These results suggested that PACE has a great potential for industrial-scale production and clinical applications.