目的: 应用往复筒法测定麝香缓释微片的体外释放度。方法: 采用气相色谱法建立缓释微片主要活性成分麝香酮的体外分析方法,比较其在不同浓度吐温-80、十六烷基三甲基溴化铵(CTAB) 及十二烷基硫酸钠(SDS)中的平衡溶解度,确定释放介质的种类,考察停留时间、滴水时间、往复速率和筛网孔径等因素对麝香酮释放行为的影响,并与桨法进行比较,同时对其释药机制进行了初步探究。结果: 所建分析方法线性良好,精密度、重复性、稳定性的RSD均小于3%,加样回收率合格。往复筒法释放介质为0.05%吐温-80 200 mL,停留和滴水时间为20 s,往复速率15 dip·min-1,上、下筛网目数分别为20和40。与桨法相比,往复筒法中麝香酮在不同pH条件下能完全释放,且释放曲线平稳递增。结论: 本研究可为往复筒法在中药缓释制剂的体外评价提供一定的参考和借鉴。
Objective: To determine the in vitro release degree of musk sustained-release mini-tablets by reciprocating cylinder method. Methods: Gas chromatography was used to establish the in vitro analysis of muscone, which is the main active ingredient of sustained-release mini-tablets. Comparing its equilibrium solubility in different concentrations of Tween-80, hexadecyl trimethyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS), to determine the type of release medium. The effects of residence time, drip time, reciprocation rate, and screen mesh sizes on the release behaviours of muscone were investigated. Results were compared with that of the paddle method. Meanwhile, a preliminary investigation into the mechanism of its release was also carried out. Results: The linearity of the constructed analytical method was better, the RSD values of precision, repeatability and stability were less than 3%, and the spiked sample recovery was qualified. The release medium for the reciprocating cartridge method was 200 mL of 0.05% Tween-80, with a dwell and drip time of 20 s, a reciprocation rate of 15 dip·min-1, and upper and lower screen mesh sizes of 20 and 40 respectively. Compared with the paddle method, Muscone was completely released under different pH conditions in the reciprocating cylinder method, and the release curve increased smoothly. Conclusion: The study can provide some references for the reciprocating cylinder method in the in vitro evaluation of sustained-release prescriptions of traditional Chinese medicine.
[1] 李伊娜,张娜,刘万卉,等.往复筒法在药物溶出度研究中的应用进展[J]. 药物分析杂志, 2021, 41 (2): 185
LI YN, ZHANG N, LIU WH, et al. Progress in applications of the reciprocating cylinder apparatus in dissolution testing of drug formulations [J]. Chin J Pharm Anal, 2021, 41 (2): 185
[2] YU LX, WANG JT, HUSSAIN AS. Evaluation of USP apparatus 3 for dissolution testing of immediate-release products[J]. AAPS Pharm Sci, 2002, 4 (1): 1
[3] 庞发根,梁爱仙,刘晶晶,等.以氟西汀迟释胶囊为例探讨往复筒溶出度测定法的基本特征[J]. 中国药品标准, 2020, 21 (2): 150
PANG FG, LIANG AX,LIU JJ, et al. Analysis on basic characteristics of reciprocating cylinder dissolution determination method with fluoxetine delayed-release capsules [J]. Drug Stand China, 2020, 21(2): 150
[4] 邓卫芳,裴晓华. 西黄丸在乳腺增生病和乳腺癌中的应用研究[J]. 新中医, 2012, 44 (12): 126
DENG WF, PEI XH. Study on the application of Xihuangwan in breast hyperplasia and breast cancer [J]. New Chin Med, 2012, 44 (12):126
[5] 洪日,吴永强,吴越. 西黄丸辅助治疗中晚期乳腺癌的疗效观察[J]. 中国中药杂志, 2014, 39 (6): 1120
HONG R, WU YQ, WU Y. Effects of Xihuangwan in assistant treatment of patients with advanced breast cancer [J]. China J Chin Mater Med, 2014, 39 (6): 1120
[6] 孙晓霞,孟静岩,王威,等. 西黄丸治疗恶性肿瘤的基础与临床研究现状[J]. 天津中医药, 2013, 30 (1): 60
SUN XX, MENG JY, WANG W, et al. Current status of basic and clinical research on Xihuangwan in the treatment of malignant tumours [J]. Tianjin J Tradit Chin Med, 2013, 30 (1): 60
[7] 王丽娟,路军章. 中医药治疗胰腺癌的研究进展[J]. 中华中医药杂志, 2016, 31(3): 961
WANG LJ, LU JZ. Research progress of treating pancreatic cancer with traditional Chinese medicine [J]. China J Tradit Chin Med Pharm, 2016, 31(3): 961
[8] 徐秋萍,胡文静,刘宝瑞. 西黄丸抗肿瘤作用的研究现状[J]. 癌症进展, 2016, 14 (1): 32
XU QP, HU WJ, LIU BR. Current status of research on the anti-tumour effects of Xihuangwan [J]. Oncol Progr, 2016, 14 (1): 32
[9] 张程荣,赵耀东. 中药复方药动学研究概述[J]. 海峡药学, 2014, 26 (10): 3
ZHANG CR, ZHAO YD. Overview of pharmacokinetic studies on Chinese medicine compounding [J]. Strait Pharm J, 2014, 26 (10): 3
[10] 李婉斯,黄潘雯,张永太,等. 基于数学模型研究SuperTab 40LL对麝香缓释微片压缩特性的影响[J]. 中国中药杂志, 2021, 46 (19): 4978
LI WS, HUANG PW, ZHANG YT, et al. Study on effect of SuperTab 40LL on compression characteristics of musk sustained-release mini-tablets based on mathematical models [J]. China J Chin Mater Med, 2021, 46 (19): 4978
[11] KÖNCZÖL Á, DARGÓ G. Brief overview of solubility methods: Recent trends in equilibrium solubility measurement and predictive models[J]. Drug Discov Today Technol, 2018,27: 3
[12] 中华人民共和国药典.四部[S]. 2020:424
ChP 2020. Vol Ⅳ [S]. 2020:424
[13] NAGATA S, JIN-NAI A, HIRAI K, et al. Evaluation of dissolution of osmotic-controlled release paliperidone tablets using the reciprocating cylinder method[J]. Yakugaku Zasshi, 2013, 133(3):405
[14] JANTRATID E, DE Maio V, RONDA E, et al. Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form[J]. Eur J Pharm Sci, 2009, 37 (3-4): 434
[15] 国家药典委员会. 中国药典分析检测技术指南[M]. 北京:中国医药科技出版社,2017:474
National Pharmacopoeia Commission. Guidance on Analysis and Testing Technology of the Chinese Pharmacopoeia [M]. Beijing: China Pharmaceutical Science and Technology Press, 2017: 474
[16] 肖娟,李瑞翔,秦晶,等. 盐酸普拉克索蜡质骨架缓释片的体外释放与在Beagle犬体内吸收的相关性[J]. 中国医药工业杂志, 2014, 45 (7): 629
XIAO J, LI RX, QIN J, et al. Correlation between in vitro release and in vivo absorption in beagle dogs of pramipexole hydrochloride extended-release tablets based on lipid matrix[J]. Chin J Pharm, 2014, 45(7): 629
[17] 保敏敏,吕蓓蓓,魏文芝,等. 奥卡西平半片制剂的往复筒溶出方法研究及分剂量评价[J]. 中国现代应用药学,2023,40 (15): 2117
BAO MM, LÜ BB, WEI WZ, et al. Study on oxcarbazepine half-tablet preparation by reciprocating cylinder method and partial dose evaluation[J]. Chin J Mod Appl Pharm, 2023, 40 (15): 2117
[18] ROHRS BR, BURCH-CLARK DL, WITT MJ, et al. USP dissolution apparatus 3 (reciprocating cylinder): instrument parameter effects on drug release from sustained release formulations [J]. J Pharm Sci, 1995, 84 (8):922
[19] YU LX, WANG JT, HUSSAIN AS. Evaluation of USP apparatus 3 for dissolution testing of immediate-release products [J]. AAPS Pharm Sci, 2002, 4 (1):E1
[20] 徐华枫.硝苯地平缓控释片释放度测定方法的探讨[D]. 上海:上海交通大学, 2019
XU HF. Investigation on the Test Method for the Release of Nifedipine Modified-Release Tablets[D]. Shanghai:Shanghai Jiao Tong University, 2019
[21] RAMOS PEZZINI B, GOMES FERRAZ H. Bio-dis and the paddle dissolution apparatuses applied to the release characterization of ketoprofen from hypromellose matrices [J]. AAPS Pharm Sci Technol, 2009, 10 (3): 763
[22] SUBBURAYALU R, KUNCHITHAPATHAM J, DEVI T. Application of biorelevant dissolution tests to the prediction of in vivo performance of clopidogrel extended release mini tablet filled in capsules [J]. Ind Am J Pharm Res, 2014, 4 (1): 160
