药学学报, 2022, 57(4): 1163-1171
引用本文:
华韵, 吴宇申, 郑道一, 翁兴业, 程冉, 衡伟利, 魏元锋, 张建军, 高缘. 共晶技术改善氯诺昔康溶出行为及可压片性的研究[J]. 药学学报, 2022, 57(4): 1163-1171.
HUA Yun, WU Yu-shen, ZHENG Dao-yi, WENG Xing-ye, CHENG Ran, HENG Wei-li, WEI Yuan-feng, ZHANG Jian-jun, GAO Yuan. Enhanced dissolution and tabletability of lornoxicam by cocrystallization[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1163-1171.

共晶技术改善氯诺昔康溶出行为及可压片性的研究
华韵1, 吴宇申1, 郑道一2, 翁兴业2, 程冉1, 衡伟利1, 魏元锋1, 张建军2, 高缘1*
1. 中国药科大学中药学院, 江苏 南京 211198;
2. 中国药科大学药学院, 江苏 南京 211198
摘要:
氯诺昔康是一种具有解热镇痛和抗炎作用的非甾体抗炎药,属于生物药剂学分类系统(BCS) II类药物,水溶性差,口服生物利用度低。此外,氯诺昔康本身的可压片性较差,限制了其口服固体制剂的开发。本研究通过减压旋转蒸发法制备氯诺昔康-葛根素共晶,以提高氯诺昔康的溶出度及可压片性。利用X-射线粉末衍射法、差示扫描量热分析、傅里叶变换红外光谱法和热重分析等手段进行表征,并对所制备共晶的溶出行为、可压片性和稳定性进行考察。粉末溶出实验及特性溶出实验表明氯诺昔康-葛根素共晶较单独氯诺昔康有更高的溶出速率。平衡溶解度实验表明,氯诺昔康-葛根素共晶可以显著提高氯诺昔康(约4.0倍)及葛根素(约1.5倍)在水中的溶解度。并且,氯诺昔康形成共晶后表现出显著改善的可压片性。稳定性实验发现,该共晶在40℃和25℃/75% RH条件下放置60天后,含量均无明显变化,化学稳定性良好。
关键词:    氯诺昔康      共晶      葛根素      溶出      可压片性      稳定性     
Enhanced dissolution and tabletability of lornoxicam by cocrystallization
HUA Yun1, WU Yu-shen1, ZHENG Dao-yi2, WENG Xing-ye2, CHENG Ran1, HENG Wei-li1, WEI Yuan-feng1, ZHANG Jian-jun2, GAO Yuan1*
1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China;
2. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
Lornoxicam (LOR) is a nonsteroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. As a biopharmaceutics classification system (BCS) class II drug, it has poor aqueous solubility and then low bioavailability after oral administration. In addition, the tabletability of LOR itself is also poor and could not form the tablet after compression, which seriously limits the development of its oral solid dosage. The current study aims to improve dissolution and tabletability of LOR by cocrystallization technique with small molecule puerarin (PUE). LOR cocrystal with the co-former PUE was prepared via the solvent-evaporation method and characterized by powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and thermo-gravimetric analyzer. The dissolution behavior, tabletability and stability of the prepared cocrystal were also further investigated. In comparison to pure LOR, LOR-PUE cocrystal showed higher apparent and intrinsic dissolution rate. Moreover, after cocrystallization, the solubility of LOR and PUE showed 4.0-fold and 1.5-fold increase compared to the raw ones in water, respectively. LOR-PUE cocrystal showed significantly improved tabletability compared to LOR alone under a wide compression range of 75-375 MPa. In addition, such cocrystal exhibited superior chemical stability with no change of drug contents for at least 60 days under the conditions of 40℃ and 25℃/75% RH.
Key words:    lornoxicam    cocrystal    puerarin    dissolution    tabletability    stability   
收稿日期: 2021-07-20
DOI: 10.16438/j.0513-4870.2021-1060
基金项目: 国家自然科学基金资助项目(82074029,81773675,81873012);中国药科大学“双一流”建设项目(CPU2018GY11,CPU2018GY27);中国博士后科学基金项目(2021M693517).
通讯作者: 高缘,Tel:86-25-83379418,E-mail:newgaoyuan@163.com
Email: newgaoyuan@163.com
相关功能
PDF(2338KB) Free
打印本文
0
作者相关文章
华韵  在本刊中的所有文章
吴宇申  在本刊中的所有文章
郑道一  在本刊中的所有文章
翁兴业  在本刊中的所有文章
程冉  在本刊中的所有文章
衡伟利  在本刊中的所有文章
魏元锋  在本刊中的所有文章
张建军  在本刊中的所有文章
高缘  在本刊中的所有文章

参考文献:
[1] Gao Y, Zu H, Zhang JJ. Pharmaceutical cocrystals[J]. Prog Chem (化学进展), 2010, 22:829-836.
[2] Gao Y, Zu H, Zhang JJ. Enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation[J]. J Pharm Pharmacol, 2011, 63:483-490.
[3] Weng XY, Pang ZT, Qian S, et al. Druggability enhancement by modification of physicochemical properties of drugs via crystal engineering[J]. Acta Pharm Sin (药学学报), 2020, 55:2883-2891.
[4] Huang YT, Zhang BW, Gao Y, et al. Baicalein-nicotinamide cocrystal with enhanced solubility, dissolution, and oral bioavailability[J]. J Pharm Sci, 2014, 103:2330-2337.
[5] Peng B, Wang JR. Advances in drug-drug complexes based on the crystal engineering design[J]. Acta Pharm Sin (药学学报), 2020, 55:2358-2367.
[6] Radhofer-Welte S, Rabasseda X.Lornoxicam, a new potent NSAID with an improved tolerability profile[J]. Drugs Today, 2000, 36:55-76.
[7] Yu B, Ding JW, Wang XA. Progress of Entresto in the treatment of heart failure[J]. Hainan Med J (海南医学), 2018, 29:1420-1422.
[8] Kidd B, Frenzel WA. Multicenter, randomized, double blind study comparing lornoxicam with diclofenac in osteoarthritis[J]. J Rheumatol, 1996, 23:1605-1611.
[9] Das SK, Banerjee M, Mondal S, et al. A comparative study of efficacy and safety of lornoxicam versus tramadol as analgesics after surgery on head and neck[J]. Indian J Otolaryngol, 2013, 65:126-130.
[10] Shah N, Patel R, Seth AK, et al. Solubility enhancement techniques as a strategy to improve the solubility of lornoxicam[J]. Pharma Sci Monit, 2015, 6:168-175.
[11] Zhou YX, Zhang H, Peng C. Puerarin:a review of pharmacological effects[J]. Phytother Res, 2014, 28:961-975.
[12] Tu LX, Yi YN, Wu W, et al. Effects of particle size on the pharmacokinetics of puerarin nanocrystals and microcrystals after oral administration to rat[J]. Int J Pharm, 2013, 458:135-140.
[13] Xiao C, Li J, Dong XX, et al. Anti-oxidative and TNF-α suppressive activities of puerarin derivative (4AC) in RAW264.7 cells and collagen-induced arthritic rats[J]. Eur J Pharmacol, 2011, 666:242-250.
[14] Qiao N, Wang K, Schlindwein W, et al. In situ monitoring of carbamazepine-nicotinamide cocrystal intrinsic dissolution behavior[J]. Eur J Pharmacol, 2013, 83:415-426.
[15] Lawrence XY, Carlin AS, Amidon GL, et al. Feasibility studies of utilizing disk intrinsic dissolution rate to classify drugs[J]. Int J Pharm, 2004, 270:221-227.
[16] Zhang JJ, Tan X, Gao J, et al. Characterization of two polymorphs of lornoxicam[J]. J Pharm Pharmacol, 2013, 65:44-52.
[17] Zhong ZY, Wu M, Qian S, et al. Inhibition of transformation from puerarin monohydrate to puerarin dihydrate by polyvinylpyrrolidones during dissolution[J]. Acta Pharm Sin (药学学报), 2017, 52:302-308.
[18] Pang ZT, Wei YF, Wang NN, et al. Gel formation of puerarin and mechanistic study during its cooling process[J]. Int J Pharm, 2018, 548:625-635.
[19] Gowda DV, Srivastava A, Aravind Ram AS, et al. Encapsulation of lornoxicam into spermaceti microspheres and comparative bioavailability study[J]. Int J Drug Deliv, 2014, 6:7-13.
[20] Tao H, Meng Q, Li M, et al. HP-β-CD-PLGA nanoparticles improve the penetration and bioavailability of puerarin and enhance the therapeutic effects on brain ischemia-reperfusion injury in rats[J]. Naunyn Schmiedebergs Arch Pharmacol, 2013, 386:61-70.
[21] Chen AZ, Li Y, Chau FT, et al. Application of organic nonsolvent in the process of solution-enhanced dispersion by supercritical CO2 to prepare puerarin fine particles[J]. J Supercrit Fluids, 2009, 49:394-402.
[22] Skjodt NM, Davies DNM. Clinical pharmacokinetics of lornoxicam[J]. Clin Pharmacokinet, 1998, 34:421-428.
[23] Wei YF, Zhang L, Wang NN, et al. Mechanistic study on complexation-induced spring and hover dissolution behavior of ibuprofen-nicotinamide cocrystal[J]. Cryst Growth Des, 2018, 18:7343-7355.
[24] Qiao N, Li M, Schlindwein W, et al. Pharmaceutical cocrystals:an overview[J]. Int J Pharm, 2011, 419:1-11.
[25] Zhou SY, Zhang BW, Wei YF, et al. Enhanced dissolution and oral bioavailability of baicalein by cocrystallization[J]. J China Pharm Univ (中国药科大学学报), 2018, 49:682-688.
[26] Cheng H, Wei YF, Wang SR, et al. Improving tabletability of excipients by metal-organic framework-based cocrystallization:a study of mannitol and CaCl2[J]. Pharm Res, 2020, 37:130.
[27] Sun CC. Decoding powder tabletability:roles of particle adhesion and plasticit[J]. J Adhes Sci Technol, 2011, 25:483-499.
[28] Wang CG, Paul S, Wang K, et al. Relationships among crystal structures, mechanical properties, and tableting performance probed using four salts of diphenhydramine[J]. Cryst Growth Des, 2017, 17:6030-6040.
相关文献:
1.吴秀娟, 庞遵霆, 杨思彤, 严梦梦, 高缘.共无定形技术改善葛根素水溶性及增溶机制研究[J]. 药学学报, 2021,56(2): 585-592
2.邱培燊, 高静, 钱帅, 魏元锋, 张建军.对乙酰氨基酚通过共晶形成提高阿德福韦酯的溶出及肠吸收[J]. 药学学报, 2018,53(6): 993-1001
3.申亚静, 覃蕾, 衡伟利, 张建军, 钱帅, 高缘.他达拉非-达泊西汀共无定形物的形成及其溶出度与稳定性的评价[J]. 药学学报, 2018,53(7): 1162-1168
4.仲昭毅, 吴敏, 钱帅, 张建军, 高缘.聚乙烯吡咯烷酮抑制葛根素一水合物在溶出过程中向二水合物的转变[J]. 药学学报, 2017,52(2): 302-308
5.严红梅, 贾晓斌, 张振海, 孙娥, 徐怡皓.氧化石墨烯固化挥发油的研究[J]. 药学学报, 2015,50(2): 222-226
6.夏学军;陶忠华;任怡;汪仁芸;刘玉玲.布格呋喃固体分散体的体外研究[J]. 药学学报, 2008,43(5): 548-552