药学学报, 2019, 54(1): 14-21
引用本文:
宋航, 高利芳, 付强, 王珏, 何仲贵. 以Soluplus为载体的固体分散体提高螺内酯体外溶出和物理稳定性[J]. 药学学报, 2019, 54(1): 14-21.
SONG Hang, GAO Li-fang, FU Qiang, WANG Jue, HE Zhong-gui. Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with Soluplus[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 14-21.

以Soluplus为载体的固体分散体提高螺内酯体外溶出和物理稳定性
宋航1, 高利芳1, 付强1, 王珏2, 何仲贵1
1. 沈阳药科大学, 辽宁 沈阳 110016;
2. 中国食品药品检定研究院包装材料与药用辅料检定所, 北京 100050
摘要:
螺内酯属于生物药剂学分类系统第Ⅱ类药物,溶解性差,口服生物利用度低。因此,本文采用溶剂法制备螺内酯固体分散体,以提高其水溶解性。基于体外溶出实验对螺内酯固体分散体进行处方优化;采用差示扫描量热法、X射线衍射法和傅里叶转换红外光谱法,确定药物在载体材料中的物理状态和药物与载体材料之间可能存在的相互作用;最后,通过影响因素试验,明确影响螺内酯固体分散体稳定性的关键因素。结果表明,在以Soluplus和HPMC-E5为载体的固体分散体中,药物均以无定型态存在,且药物与载体之间均存在氢键相互作用。因此,其体外溶出速度显著提高。影响因素试验表明,以Soluplus为载体的固体分散体,其物理稳定性优于以HPMC-E5为载体的固体分散体。因此,通过溶剂法制备螺内酯-Soluplus固体分散体可以提高其体外溶出速度和物理稳定性。
关键词:    螺内酯      溶剂法      固体分散体      载体材料      物理稳定性     
Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with Soluplus
SONG Hang1, GAO Li-fang1, FU Qiang1, WANG Jue2, HE Zhong-gui1
1. Shenyang Pharmaceutical University, Shenyang 110016, China;
2. Institute of Packaging Materials and Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing 100050, China
Abstract:
Spironolactone, a class Ⅱ drug of the biopharmaceutics classification system, has low oral bioavailability due to poor solubility. Spironolactone solid dispersions were prepared using the solvent method in order to improve its aqueous solubility. Optimization studies of spironolactone solid dispersions were performed using in vitro dissolution tests. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared were used to investigate the physical state of the drug in carrier materials and to detect the possible interactions between the drug and carrier materials in the solid dispersions. In addition, stress tests were employed to elucidate the key factors which have influence on the stability of the spironolactone solid dispersions. Results showed that spironolactone in the solid dispersions formulated with Soluplus and HPMC-E5 were both in amorphous state and the hydrogen bonds between the drug and carrier materials were formed in the solid dispersion. Therefore, the in vitro dissolution of spironolactone was also significantly enhanced. Stress tests demonstrated that the physical stability of spironolactone solid dispersions prepared with Soluplus was greatly improved compared to those formulated with HPMC-E5. Thus, spironolactone solid dispersion formulated with Soluplus using the solvent method could be used to improve the in vitro dissolution and stability of poorly soluble drugs.
Key words:    spironolactone    solvent method    solid dispersion    carrier material    physical stability   
收稿日期: 2018-10-22
DOI: 10.16438/j.0513-4870.2018-0958
基金项目: 国家自然科学基金资助项目(81502993);辽宁省自然科学基金资助项目(20170540842);辽宁省教育厅高校基本科研项目(2017LQN02).
通讯作者: 付强,Tel/Fax:86-24-23986325,E-mail:fuqiang@syphu.edu.cn;王珏,Tel:86-10-67095126,E-mail:myxwj2007@163.com
Email: fuqiang@syphu.edu.cn;myxwj2007@163.com
相关功能
PDF(752KB) Free
打印本文
0
作者相关文章
宋航  在本刊中的所有文章
高利芳  在本刊中的所有文章
付强  在本刊中的所有文章
王珏  在本刊中的所有文章
何仲贵  在本刊中的所有文章

参考文献:
[1] Kerns EH. High throughput physicochemical profiling for drug discovery[J]. J Pharm Sci, 2001, 90:1838-1858.
[2] Yue PF, Liu Y, Xie J, et al. Review and prospect on preparation technology of drug nanocrystals in the past thirty years[J]. Acta Pharm Sin (药学学报), 2018, 53:529-537.
[3] Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs[J]. Drug Discov Today, 2007, 12:1068-1075.
[4] Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems[J]. J Pharm Sci, 1971, 60:1281-1302.
[5] Chen MW, Chen WR, Chen TK, et al. Application research of hot-melt extrusion in preparation of solid dispersion[J]. Acta Pharm Sin (药学学报), 2012, 47:163-167.
[6] Kim EJ, Chun MK, Jang JS, et al. Preparation of a solid dispersion of felodipine using a solvent wetting method[J]. Eur J Pharm Biopharm, 2006, 64:200-205.
[7] Wu JX, Yang M, van den Berg F, et al. Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability[J]. Eur J Pharm Sci, 2011, 44:610-620.
[8] Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods[J]. Int J Pharm, 2004, 272:1-10.
[9] Munjal M, Stodghill SP, ElSohly MA, et al. Polymeric systems for amorphous Δ9-tetrahydrocannabinol produced by a hot-melt method. Part I:Chemical and thermal stability during processing[J]. J Pharm Sci, 2006, 95:1841-1853.
[10] Shah S, Maddineni S, Lu J, et al. Melt extrusion with poorly soluble drugs[J]. Int J Pharm, 2013, 453:233-252.
[11] Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure[J]. New Engl J Med, 1999, 341:709-717.
[12] Lula I, Gomes MF, Piló-Veloso D, et al. Spironolactone and its complexes with β-cyclodextrin:modern NMR characterization and structural DFTB-SCC calculations[J]. J Incl Phenom Macrocycl Chem, 2006, 56:293-302.
[13] Zhu L, Yang M, Zhang Q, et al. Preparation of posaconazole solid dispersion via hot-melt extrusion and preliminary evaluation in vitro[J]. J China Pharm Univ (中国药科大学学报), 2015, 46:309-315.
[14] Yun F, Kang A, Shan J, et al. Preparation of osthole-polymer solid dispersions by hot-melt extrusion for dissolution and bioavailability enhancement[J]. Int J Pharm, 2014, 465:436-443.
[15] Sarode AL, Sandhu H, Shah N, et al. Hot melt extrusion (HME) for amorphous solid dispersions:predictive tools for processing and impact of drug-polymer interactions on supersaturation[J]. Eur J Pharm Sci, 2013, 48:371-384.
[16] Crowley MM, Fredersdorf A, Schroeder B, et al. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films[J]. Eur J Pharm Sci, 2004, 22:409-418.
[17] Xiang WJ, Guo XR, Han J. Application of solubility parameters in solid dispersions[J]. Pharm Today (今日药学), 2010, 20:5-8.
[18] Just S, Sievert F, Thommes M, et al. Improved group contribution parameter set for the application of solubility parameters to melt extrusion[J]. Eur J Pharm Biopharm, 2013, 85:1191-1199.
相关文献:
1.陈美婉, 陈文荣, 陈桐楷, 陈锐娥, 王一涛.热熔挤出技术制备固体分散体的应用研究[J]. 药学学报, 2012,47(2): 163-167