Xia Xue-Jun, Guo Rui-Fang, Liu Yu-Ling, Zhang Peng-Xiao, Zhou Cui-Ping, Jin Du-Jia, Wang Ren-Yun
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chem Pharm Bull (Tokyo). 2011;59(3):321-6. doi: 10.1248/cpb.59.321.
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, pH 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 383 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115 °C for 30 min and remained stable for at least 12 months at 6 °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.
本文的目的是开发一种新型的无聚氧乙烯蓖麻油、可高压灭菌的紫杉醇静脉乳剂（PACE）。使用紫杉醇 - 胆固醇复合物作为药物载体，以提高紫杉醇在乳剂油相中的溶解度。该复合物和PACE分别通过旋转蒸发和高压均质法制备。研究了油相、乳化剂和pH值对PACE特性的影响。对PACE的外观、形态、渗透压、pH值、粒径、zeta电位、包封率和稳定性进行了表征。通过豚鼠过敏反应评估超敏反应。最终制剂由复合物、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383 mOsmol/kg和4.5。该制剂在115℃下高压灭菌30分钟后仍能存活，在6℃下至少稳定12个月。在豚鼠中，PACE也比等剂量的基于聚氧乙烯蓖麻油的紫杉醇注射液表现出更好的耐受性，因为未观察到明显的超敏反应。这些结果表明，PACE具有很大的工业规模生产和临床应用潜力。
