Gemcitabine hydrochloride thermosensitive gel injection preparation and contents determination
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摘要: 目的 制备吉西他滨温敏凝胶注射剂,并建立其含量测定方法。 方法 以聚乙二醇/聚酯嵌段共聚物(PLGA-PEG-PLGA)为载体,制备吉西他滨温敏凝胶注射剂,采用1H NMR、FT-IR对其结构进行表征, HPLC法测定其中药物的含量。 结果 吉西他滨温敏凝胶注射剂中,PLGA-PEG-PLGA的质量分数为20%,吉西他滨含量为40 mg/ml,胶凝温度为(37±0.15) ℃,在接近人体温度时黏度最大;吉西他滨在5~500 μg/ml范围内线性关系良好(r=0.999 8),精密度和重复性良好,溶液24 h内稳定性良好,低、中、高浓度的吉西他滨的回收率分别为(99.5±3.2)%、(100.4±2.4)%、(102.1±2.4)%,n=3。3批样品中吉西他滨的平均含量分别为标示量的(101.87±2.95)%、 (99.4±2.73)%、(98.98±0.71)%,n=3。 结论 采用PLGA-PEG-PLGA聚合物为载体制备的吉西他滨温敏凝胶注射剂质量可控,是一种很有开发前景的抗胰腺癌制剂。
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关键词:
- 吉西他滨 /
- 聚乙二醇/聚酯嵌段共聚物 /
- 温敏凝胶 /
- 含量测定
Abstract: Objective To prepare gemcitabine hydrochloride thermosensitive gel injection and to stablish the determination methods of its contents. Methods Gemcitabine hydrochloride thermosensitive gel injection was prepared using PLGA-PEG-PLGA as thermosensitive viecle. The contents of gemcitabine hydrochloride were determined by HPLC. Results The formulation contained 40 mg/ml gemcitabine and 20% (wt) PLGA-PEG-PLGA with phase-transition temperature of (37±0.15) ℃, showing the best viscosity around human body temperature. Gemcitabine hydrochloride presented a good linearity in the range of 5-500 μg/ml(r=0.999 8), which had good precision and reproducibility. The recovery rate of low, middle and high concentrations of gemcitabine hydrochloride were (99.5±3.2)%, (100.4±2.4)%, (102.1±2.4)%,n=3, respectively. The average contents of gemcitabine hydrochloride in three batches of sample were (101.87±2.95)%, (99.4±2.73)%, (98.98±0.71)%, n=3, respectively. Conclusion The quality of gemcitabine hydrochloride thermosensitive gel injection with PLGA-PEG-PLGA as matrix could be controlled. It is a promising new drug for pancreatic cancer.-
Key words:
- gemcitabine hydrochloride /
- PLGA-PEG-PLGA /
- thermosensitive gel /
- content determination
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[1] Cascium S, Craziano F, Catalana G. Chemotherapy for ad-vanced pancreatic cancer: It may no longer be ignored [J]. Ann Oncol,1999,10(1):105. [2] Saif MW.A new developments in the treatment of pancreatic cancer[J]. Highlights from the “ 44th ASCO Annual Meet-ing”.Chicago,IL,USA.May 30-June 3,2008.JOP 2008, 9:391-397. [3] Tanaka M,Javle M,Dong X, et al.Gemcitabine metabolic and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients locally pancreatic cancer [J]. Cancer,2010,116(22):5325-5335. [4] Vervenne W,Bennouna J,Humblet Y,et al.A randomized, double blind,placebo controlled multicenter phase III trial to evaluate the efficacy and safety of adding bevacizumab to erlo-tinib and gemcitabine in patients with metastatic pancreatic cancer[J].J Clin Oncol,2008,26(suppl):4507. [5] Okino H, Maeyama R, Manabe T. Trans-tissue, sustained release of gemcitabine from photo cured gelatin gel inhibits the growth of heterotopic human pancreatic tumor in nude mice[J].Cli Cancer Res.2003,9 (15):5786-5793. [6] Rosemurgy AS,Serafini FM. New directions in systemic therapy of pancreatic cancer [J]. Cancer Control, 2000,7 (5):437-51. [7] Howell SB.Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoamTM technology[J].Cancer J 2001,7(3):219-227. [8] Kim YJ, Kim SW. Controlled drug delivery from injectable biodegradable triblock copolymer [M]. Washington:Ameri-can Chemical Society,2003:300-311. [9] Jeong B,Bae YH.Biodegradable block copolymers as inject-able drug-delivery systems [J]. Nature,1997, 388 (6645): 860-862. [10] 杨 梅,李井泉,汤致强。PLGA 吉西他滨缓释微球在荷胰腺 癌裸鼠体内的药动学研究[J].中国药学杂志,2010,45 (4): 295-299.
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