目的研究塞克硝唑苯甲酸酯(secnidazole benzoate,SBZ)与羟丙基-β-环糊精(hydroxylpropyl-β-cyclodextrin,HP-β-CD)在水溶液中的包合作用、包合比及包合过程中的热力学参数变化。方法分别采用相溶解度法、紫外吸收分光光度法、等摩尔系列法等方法测定SBZ与HP-β-CD在水溶液中包合作用、包合比及包合过程中的热力学参数变化。结果在不同pH值的缓冲液中,SBZ与HP-β-CD均可形成1∶1包合物;热力学参数显示包合过程为焓推动的熵减过程,可自发进行(△G<0)。结论SBZ与HP-β-CD在水溶液中可自发形成摩尔比为1∶1的包合物,从而增加其溶解度。选择适宜的包合温度及合适的pH值将有利于包合过程的进行。
Abstract
OBJECTIVE To investigate the complexation of secnidazole benzoate with hydroxylpropyl-β-cyclodextrin (HP-β-CD) in aqueous solutions, inclusion molar radio of the host to guest molecules and change of thermodynamic parameters during the complexation process. METHODS The complexation mechanism, inclusion molar ratio of the host to guest molesules and change of thermodynamic parameters were measured by phase solubility method, UV spectrophotometry, and equimolar series method, respectively. RESULTS The 1∶1 molar ratio inclusion complex was obtained in various pH buffered solutions. The inclusion process was induced automatically along with the release of heat and the decrease of entropy. CONCLUSION An 1∶1 molar ratio inclusion complex of secnidazole benzoate with HP-β-CD could be formed spontaneously. The solubility of secnidazole benzoate in aqueous solution was increased. Appropriate temperature and suitable media pH probably favor the progress of the inclusion process.
关键词
塞克硝唑苯甲酸酯 /
羟丙基-β-环糊精 /
包合比 /
包合作用 /
热力学参数
{{custom_keyword}} /
Key words
secnidazole benzoute /
hydroxylpropyl-β-cyclodextrin /
complexation ratio /
complexation /
thermodynamic parameter
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] JABER SANTIAGO A B. Alkanoic and benzoic esters of 1-(2-hydroxypropyl)- 2-methy-5-nitro-imidazole: USA, 5574167[P]. 1996-12-12.
[2] DING P T, WU X M. A new pharmaceutical excipient 2-hydroxylpropyl- β-cyclodextrin [J]. World Notes Antibiot (Biochem Pharm Division)(国外医药?合成药生化药制剂分册),1996,17(2):107-111.
[3] GU F G, CUI F D, GAO Y L. The complexation of prostaglandin E1 with hydroxylpropyl-β-cyclodextrin in aqueous solution[J]. Acta Pharm Sin（药学学报），2004，39（9）:742-746.
[4] HIGUCHI T, CONNORS K A. Phase solubility techniques[J]. Adv Anal Chem Instrum, 1965,4(1):117-212.
[5] TONG L H. Chemistry of Cyclodextrin : Basics and Applications（环糊精化学——基础与应用）[M]. Vol 1. Beijing：Science Press，2001：164.
[6] FAN Y X, LI J F, DONG C. Preparation and study on the inclusion complexes of two tanshinone compounds with b-cyclodextrin[J]. Spectrochimica Acta Part A, 2005, 61(1):135-140.
[7] LOUKAS Y L. Evaluation of the methods for the determination of the stability constant of cyclodextrinchlorambucil inclusion complexes [J]. J Pharm Biomed Anal, 1997,16(2):275-280.
[8] TONG L H. Chemistry of Cyclodextrin：Basics and Applications(环糊精化学——基础与应用)[M].Vol 1.Beijing：Science Press，2001: 135-137.
[9] MARTIN E M, DEL VALLE D M M.Cyclodextrins and their uses: a review [J]. Process Biochem, 2004, 39(9)：1033-1046.
[10] CHEN X Y, LIU W Y, ZHANG J. Study on the characterization of b-cyclodextrin-diferrocenylenone inclusion complex and micro- environmental effects [J]. Spectrosc Spectral Anal(光谱学与光谱分析), 2006，26(7)：1285-1289.
[11] LI H, LIU H J, WEN Y Z, et al. Inclusion interaction of cyclodextrins and 2,4-dichlorprop methyl ester enantiomers by UV spectra[J]. J Zhejiang Univ (Agric Life Sci)(浙江大学学报，农业与生命科学版)，2008，34（1）：50-56.
[12] CUI H M, ZHANG C G, WU F L. Identification of inclusion complex of Eb with hydroxylpropyl beta cyclodextrin and investigation of its including mechanism[J]. Chin Pharm J (中国药学杂志), 2007, 42(10): 765-769.
[13] SCHNEIDERMAN E, STALCUP A M. Cyclodextrins: a versatile tool in separation science[J]. Chromatogr B, 2000, 745(1): 83-102.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
