硫酸软骨素片和胶囊试验总结20230927

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硫酸软骨素片/胶囊试验总结

接上次2023年8月30日总结，本次总厚试验内容包括咔唑浓度优化选择，硫酸软骨素片溶出曲线，胶囊回收率试验以及CPC法方法摸索。

一、检测方法优化

检测方法接着8月份的正交试验结果，对咔唑浓度进行了优化，试验结果见表1

表1正交试验结果直观分析C（mg/ml）A

0.7吸光0.6度0.5A0.40.30.20.1000.51浓度C（mg/ml）1.520.50.60.70.80.91.01.21.41.60.4520.4990.5490.5590.5820.5780.5890.5910.590

图1咔唑浓度与吸光度关系图

结论：从上图可知，咔唑浓度选择1.2mg/ml，吸光度值处于平台中期，试验结果相对稳定。因此确定方法条件如下：

对照品溶液的制备：取硫酸软骨素对照品0.1g，缜密称定，置100ml量瓶中，加水溶解并稀释至刻度，摇匀，即得（每1ml中硫酸软骨素含1mg）。

标准曲线的制备缜密量取对照品溶液0.5ml、1ml、1.5ml、2ml、2.5ml分别置于10ml容量瓶中，用水稀释至刻度，摇匀，配制硫酸软骨素系列浓度溶液，再分别取各溶液1ml置10ml试管中，加硫酸6ml，摇匀，置沸水浴中20min，取出放于冰水浴中冷却后，均加咔唑溶液（取咔唑0.12g，缜密称定，置于100ml量瓶中，加无水乙醇溶解并稀释至刻度）0.2ml，摇匀，置沸水浴中15min取出置冰水浴中至室温，以相应试剂为空白，照紫外-可见分光光度法（中国药典2023

年版二部附录ⅣA），于520nm波优点测吸光度。以浓度为横坐标，吸光度为纵坐标绘制标准曲线。

测定取本品，照溶出度测定法(中国药典2023年版二部附录ⅩC其次法，胶囊照第一法)，以水900ml为溶出介质，转速为每分钟75转，依法操作，45分钟时，取溶液适量，滤过，取续滤液2ml，用溶出介质稀释至10ml，照标准曲线的制备项下的方法，依法测定吸光度。从标准曲线上读出供试品溶液的浓度，计算溶出度。

二、硫酸软骨素片与参比制剂溶出曲线比较结果

表2硫酸软骨素片溶出度检测结果序号溶出度/％5min硫酸软骨素片自制品/水15min20min30min45min60min5min硫酸软骨素片市售品/水15min20min30min45min60min硫酸软骨素片自制品/pH1.0盐酸硫酸软骨素片市售品/pH1.0盐酸硫酸软骨素自制片/pH4.05min15min20min30min45min60min5min15min20min30min45min60min5min15min20min30min136.0786.2399.99101.10101.33103.6534.08112.14100.28105.1698.60102.8915.8744.5157.8878.7796.7198.8014.5148.5965.8166.0485.89108.6332.2978.8296.7598.99238.2290.42100.36101.03101.70100.4527.7875.6288.98101.54112.74105.6010.6733.7543.9662.0980.5794.4816.4356.4364.2599.71102.8299.6432.0082.0096.3597.71337.1189.96101.53102.36102.76100.9229.4680.43100.2297.5399.12103.2517.0352.9167.2486.5097.8798.6716.6857.0974.2492.85102.8699.6832.5882.4495.0696.70磷酸盐缓冲液硫酸软骨素市售片/pH4.0磷酸盐缓冲液硫酸软骨素自制片/pH6.8醋酸盐缓冲液硫酸软骨素片市售品/pH6.8醋酸盐缓冲液45min60min5min15min20min30min45min60min5min15min20min30min45min60min5min15min20min30min45min60min99.0798.7331.5177.09102.79109.99112.08110.7334.4367.2081.1399.7499.3997.7117.9958.5180.7391.2989.7498.88101.1197.4632.3786.4494.60113.82116.64115.6826.8956.7268.9289.01101.13100.2019.1250.5266.0292.5697.5193.3196.4799.8629.1785.28103.90109.0390.52110.5534.2168.3781.5795.8199.80100.6224.2578.3483.4492.5185.2493.58硫酸软骨素片在水中溶出曲线1202308060402000

市售品自制片20406080

硫酸软骨素片在pH1.0HCl中溶出曲线120230806040200020406080市售品自制片

硫酸软骨素片在pH4.0醋酸盐缓冲液中溶出曲线140120230806040200020406080市售自制硫酸软骨素片在pH6.8磷酸盐缓冲液中溶出曲线1202308060402000

表3硫酸软骨素片与上市品溶出曲线相像因子比较溶出介质F2水66.580.1mol/l盐酸51.19pH4.076.08PH6.861.07市售自制20406080三、硫酸软骨素胶囊回收率结果见下表：

表4硫酸软骨素胶囊回收率溶出介质原料参与量/mg38.5138.8438.92100%55.1555.4355.54130%71.571.4971.72水中其次次70%38.2638.4638.63100%54.7755.1355.23130%71.5071.4371.52PH1.0盐酸70%38.813939.05100%54.7955.0455.28130%71.6471.6971.79PH4.0醋酸盐缓冲液70%38.3638.3438.5100%55.4155.956.24130%71.5371.6971.76PH6.8磷70%38.21A测得量/mg42.0045.0541.4958.7858.5261.0476.3477.1277.6439.3340.2440.9856.0452.7358.3574.0772.3373.4043.2844.6744.8561.7561.2063.0579.9581.8080.0441.3540.6044.2362.5959.1363.4579.6082.7781.0439.18回收率（％）109.0115.9106.6106.6105.6110.0106.8107.9108.3102.8104.6106.09102.395.64105.6103.6101.3102.6111.5114.5114.9112.7111.2114.1111.6115.0111.5114.6112.8114.1113.2113.4114.2111.9111.4114.691.62101.91.93111.13.34112.91.32102.73.01108.52.87平均回RSD（％）收率（％）水70%0.4850.5200.4790.6780.6750.7040.880.8890.8950.4730.4840.4930.6750.6350.7030.8930.8720.8850.4730.4880.490.6730.6670.6870.870.890.8710.4350.4270.4650.6560.620.6650.8330.8660.8480.461

酸盐缓冲液100%38.4439.1754.7355.5856.07130%71.3471.2971.660.4690.4790.6450.6740.6940.8490.8460.84439.8540.6954.6157.0458.7271.7171.4671.2994.9096.5493.9994.1894.3292.4792.1394.62总结：胶囊回收率在pH1.0盐酸和pH4.0缓冲盐中回收率结果不理想，重复试验结果同样，原因有待查明。

同时溶出曲线对比研究试验正在进行中。

四、用CPC法测定方法学

测定方法：

滴定液：取2.0g的一水合十六烷基氯化吡啶，缜密称定，置1000ml量瓶，用水溶解并稀释至刻度，用前超声波脱气。

供试品溶液：取硫酸软骨素钠片样品研细，称取适量，用溶出介质溶解并稀释制成浓度约为0.22mg/ml的溶液，同法制备两份。

对照品溶液同法制备。C.测定

?缜密量取两份对照品溶液分别置两只锥形瓶，每份40ml。?缜密量取每份供试品溶液40ml，分别置两只锥形瓶中。

?在磁力搅拌下，用滴定液分别滴定，溶液逐渐变浑浊，当溶液变澄清并

有类白色的沉淀悬浮在溶液中时为终点。

D.计算公式

P?V1?W0?Z×100%

V0?W1?(100%?h)式中P：硫酸软骨素含量，%；

V0：对照品溶液消耗滴定液的体积，ml；V1：供试品溶液消耗滴定液的体积，ml；W0：对照品的重量，g；W1：供试品的重量，g；

h：供试品的枯燥失重，%；

Z：对照品的含量。

表6用CPC法测定硫酸软骨素片的回收率70%V17.457.497.4510.46水100%10.4810.4913.61130%13.613.675.7570%5.75.7pH1.0盐酸7.97100%8.038.0910.3130%10.3210.37.0270%pH4.0醋酸盐缓冲液7.17.0110.1100%10.051013.05130%12.9712.997.270%pH6.8磷酸盐缓冲液7.187.1110.17100%10.310.1713.24130%13.2913.15V010.4810.4810.4810.4810.4810.4810.4810.4810.488.0658.0658.0658.0658.0658.0658.0658.0658.0659.8959.8959.8959.8959.8959.8959.8959.8959.89510.310.310.310.310.310.310.310.310.3W044.3644.3644.3644.3644.3644.3644.3644.3644.3644.3844.3844.3844.3844.3844.3844.3844.3844.3844.0744.0744.0744.0744.0744.0744.0744.0744.0744.3544.3544.3544.3544.3544.3544.3544.3544.35W130.5531.0730.4843.6543.844.3557.3257.3357.8430.5530.8430.8744.2544.2844.457.3857.5757.1730.7630.7830.8444.1744.4943.9957.657.6857.2430.7130.69