与烟酸形成共晶改善法莫替丁溶解性研究

张燕, 朱玉苹, 张帅华, 周星彤, 于毓

中国药学杂志 ›› 2019, Vol. 54 ›› Issue (13) : 1054-1059.

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中国药学杂志 ›› 2019, Vol. 54 ›› Issue (13) : 1054-1059. DOI: 10.11669/cpj.2019.13.003
论著

与烟酸形成共晶改善法莫替丁溶解性研究

  • 张燕1,2, 朱玉苹3, 张帅华3, 周星彤2, 于毓2
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Improving Solubility of Famotidine by Cocrystal Synthesis with Nicotinic Acid

  • ZHANG Yan1,2, ZHU Yu-ping3, ZHANG Shuai-hua3, ZHOU Xing-tong2, YU Yu2
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摘要

目的 应用共晶技术提高法莫替丁的溶解性。方法 选择烟酸作为共晶形成物(CCF)与法莫替丁采用挥发法制备共晶,获得的共晶采用X射线单晶衍射测定单晶结构,通过X射线粉末衍射法(PXRD)、红外光谱法(IR)、差示扫描量热法(DSC)、热重法(TGA)对共晶进行检测,同时考察了共晶的溶解性和稳定性。结果 法莫替丁-烟酸共晶的不对称单元包含1个法莫替丁分子、1个烟酸分子和1个水分子,通过氢键相互连接。共晶具有特征的熔点、PXRD、IR 图谱。共晶在水中的最大溶解度比法莫替丁提高了4.2倍,并且未改变法莫替丁在人工胃液、光照、高温、高湿条件下的稳定性。结论 制备的法莫替丁-烟酸共晶明显提高了法莫替丁在水中的溶解度,为应用共晶技术提高药物水溶性提供了研究基础。

Abstract

OBJECTIVE This study was focused on obtaining and characterizing cocrystal of famotidine to improve its solubility. METHODS A new cocrystal of famotidine with nicotinic acid(FAM-NIC) was obtained by solution evaporation. And the FAM-NIC cocrystal was characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the solubility and stability of cocrystal were studied. RESULTS The asymmetric unit of FAM-NIC consisted of one molecule of famotidine, nicotinic acid, and water, and they were connected through hydrogen bonds. FAM-NIC had unique thermal, spectroscopic, X-ray diffraction, and solubility properties that differed from famotidine. Dissolution studies of the cocrystal showed a 4.2-fold increase of famotidine solubility, and FAM-NIC didn′t change the stability of famotidine in artificial gastric juice, at high humidity, at high temperature, and under illumination. CONCLUSION The new cocrystal of famotidine with nicotinic acid obviously enhanced the solubility of famotidine.And the RESULTS can be useful for improving solubility of drugs by cocrystal synthesis.

关键词

共晶 / 法莫替丁 / 烟酸 / 溶解性

Key words

cocrystal / famotidine / nicotinic acid / solubility

引用本文

导出引用
张燕, 朱玉苹, 张帅华, 周星彤, 于毓. 与烟酸形成共晶改善法莫替丁溶解性研究[J]. 中国药学杂志, 2019, 54(13): 1054-1059 https://doi.org/10.11669/cpj.2019.13.003
ZHANG Yan, ZHU Yu-ping, ZHANG Shuai-hua, ZHOU Xing-tong, YU Yu. Improving Solubility of Famotidine by Cocrystal Synthesis with Nicotinic Acid[J]. Chinese Pharmaceutical Journal, 2019, 54(13): 1054-1059 https://doi.org/10.11669/cpj.2019.13.003
中图分类号: R914   

参考文献

[1] BAVISHI D D, BORKHATARIA C H . Spring and parachute: how cocrystals enhance solubility[J]. Prog Cryst Growth Charoct, 2016, 62(3):1-8.
[2] WILLIAMS H D, TREVASKIS N L, CHARMAN S A, et al . Strategies to address low drug solubility in discovery and development[J]. Pharmacol Rev,2013, 65 (1):315-499.
[3] QIAON, LI M, SCHLINDWEIN W, et al. Pharmaceutical cocrystals: an overview[J]. Int J Pharm, 2011, 419(1):1-11.
[4] MIROSHNYK I, MIRZA S, SANDLER N. Pharmaceutical co-crystals-an opportunity for drug product enhancement[J]. Expert Opin Drug Deliv, 2009, 6(4):333-341.
[5] LIN Y, YANG H, YANG C, et al.Preparation, characterization, and evaluation of dipfluzine-benzoic acid co-crystals with improved physicochemical properties[J]. Pharm Res, 2014, 31(3):566-578.
[6] SANPHUI P, GOUD N R, KHANDAVILLI U B R, et al. Fast dissolving curcumin cocrystals[J]. Cryst Growth Des, 2011, 11(9):4135-4145.
[7] PARK B, YOON W, YUN J, et al. Emodin-nicotinamide (1∶2) cocrystal identified by thermal screening to improve emodin solubility[J]. Int J Pharm, 2019, 557(1):26-35.
[8] GANGAVARAM K, SURESH S, PAL S G, et al. Novel furosemide cocrystals and selection of high solubility drug forms [J]. J Pharm Sci, 2012, 101(2):664-680.
[9] MCNAMARA D P, CHILDS S L, GIORDANO J, et al. Use of a glutaricacid cocrystal to improve oral bioavailability of a low solubility API[J]. Pharm Res, 2006, 23(8):1888-1897.
[10] FLEISCHMAN S G, KUDUVA S S, MCMAHON J A, et al. Crystal engineering of the composition of pharmaceutical phases: multiple-component crystalline solids involving carbamazepine[J]. Cryst Growth Des, 2003, 3(6):909-919.
[11] GAO Y, ZU H, ZHANG J. Enhanced dissolution and stability of adefovirdipivoxil by cocrystal formation[J]. J Pharm Pharmacol, 2011, 63(4):483-490.
[12] ZENG Q Z, OUYANG J, ZHANG S, et al. Structural characterization and dissolution profile of mycophenolic acid cocrystals[J]. Eur J Pharm Sci, 2017,102(1):140-146.
[13] KALE D P, ZODE S S, BANSAL A K. Challenges in translational development of pharmaceutical cocrystals[J]. J Pharm Sci, 2017, 106(2):457-470.
[14] DUGGIRALA N K, PERRY M L, ALMARSSON Ö, et al. Pharmaceutical cocrystals: along the path to improved medicines[J]. Chem Commun, 2016, 52(4):640-655.
[15] ROUX M V, DAVALOS J Z, JIMENEZ P. Effect of pressure on the polymorphic forms of famotidine [J]. Thermochim Acta,2002, 394(1-2):19-24.
[16] NEMET Z, HEGEDUS B, JR C S, et al. Pressurization effects on the polymorphic forms of famotidine[J]. Thermochim Acta, 2005, 430(1-2):35-41.
[17] ISLAM M S, NARURKAR M M. Solubility, stability and ionization behaviour of famotidine[J]. J Pharm Pharmacol, 2011, 45(8):682-686.
[18] SULEIMAN M S, NAJIB N M, HASSAN M A, et al. Kinetics of the acid-catalyzed hydrolysis of famotidine[J]. Int J Pharm, 1989, 54(1):65-69.
[19] HASSAN M A, SULEIMAN M S, NAJIB N M. Improvement of the in vitro dissolution characteristics of famotidine by inclusion in β-cyclodextrin[J]. Int J Pharm, 1990, 58(1):19-24.
[20] SHI X J,GAO J,LIU Z, et al. Enhanced dissolution of famotidine by cocrystal formation with tartaric acid and maleic acid[J]. J China Pharm Univ(中国药科大学学报), 2013,44(2):124-129.
[21] SHELDRICK G M. A short history of SHELX[J]. Acta Crystallogr Sect A, 2008, 64(1):112-122.
[22] CHADHA R, BHANDARI S, HANEEF J, et al. Cocrystals of telmisartan: characterization,structure elucidation, in vivo and toxicity studies[J]. Cryst Eng Comm,2014, 16(36):8375-8389.
[23] SCHULTHEISS N, NEWMAN A. Pharmaceutical cocrystals and their physicochemical properties[J]. Cryst Growth Des, 2009, 9(6):2950-2967.

基金

国家科技重大专项-重大新药创制(2017ZX09101001)
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