硫酸軟骨素片和膠囊試驗(yàn)總結(jié)20230927

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硫酸軟骨素片/膠囊試驗(yàn)總結(jié)

接上次2023年8月30日總結(jié)，本次總厚試驗(yàn)內(nèi)容包括咔唑濃度優(yōu)化選擇，硫酸軟骨素片溶出曲線(xiàn)，膠囊回收率試驗(yàn)以及CPC法方法摸索。

一、檢測(cè)方法優(yōu)化

檢測(cè)方法接著8月份的正交試驗(yàn)結(jié)果，對(duì)咔唑濃度進(jìn)行了優(yōu)化，試驗(yàn)結(jié)果見(jiàn)表1

表1正交試驗(yàn)結(jié)果直觀分析C（mg/ml）A

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

圖1咔唑濃度與吸光度關(guān)系圖

結(jié)論：從上圖可知，咔唑濃度選擇1.2mg/ml，吸光度值處于平臺(tái)中期，試驗(yàn)結(jié)果相對(duì)穩(wěn)定。因此確定方法條件如下：

對(duì)照品溶液的制備：取硫酸軟骨素對(duì)照品0.1g，縝密稱(chēng)定，置100ml量瓶中，加水溶解并稀釋至刻度，搖勻，即得（每1ml中硫酸軟骨素含1mg）。

標(biāo)準(zhǔn)曲線(xiàn)的制備縝密量取對(duì)照品溶液0.5ml、1ml、1.5ml、2ml、2.5ml分別置于10ml容量瓶中，用水稀釋至刻度，搖勻，配制硫酸軟骨素系列濃度溶液，再分別取各溶液1ml置10ml試管中，加硫酸6ml，搖勻，置沸水浴中20min，取出放于冰水浴中冷卻后，均加咔唑溶液（取咔唑0.12g，縝密稱(chēng)定，置于100ml量瓶中，加無(wú)水乙醇溶解并稀釋至刻度）0.2ml，搖勻，置沸水浴中15min取出置冰水浴中至室溫，以相應(yīng)試劑為空白，照紫外-可見(jiàn)分光光度法（中國(guó)藥典2023

年版二部附錄ⅣA），于520nm波優(yōu)點(diǎn)測(cè)吸光度。以濃度為橫坐標(biāo)，吸光度為縱坐標(biāo)繪制標(biāo)準(zhǔn)曲線(xiàn)。

測(cè)定取本品，照溶出度測(cè)定法(中國(guó)藥典2023年版二部附錄ⅩC其次法，膠囊照第一法)，以水900ml為溶出介質(zhì)，轉(zhuǎn)速為每分鐘75轉(zhuǎn)，依法操作，45分鐘時(shí)，取溶液適量，濾過(guò)，取續(xù)濾液2ml，用溶出介質(zhì)稀釋至10ml，照標(biāo)準(zhǔn)曲線(xiàn)的制備項(xiàng)下的方法，依法測(cè)定吸光度。從標(biāo)準(zhǔn)曲線(xiàn)上讀出供試品溶液的濃度，計(jì)算溶出度。

二、硫酸軟骨素片與參比制劑溶出曲線(xiàn)比較結(jié)果

表2硫酸軟骨素片溶出度檢測(cè)結(jié)果序號(hào)溶出度/％5min硫酸軟骨素片自制品/水15min20min30min45min60min5min硫酸軟骨素片市售品/水15min20min30min45min60min硫酸軟骨素片自制品/pH1.0鹽酸硫酸軟骨素片市售品/pH1.0鹽酸硫酸軟骨素自制片/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磷酸鹽緩沖液硫酸軟骨素市售片/pH4.0磷酸鹽緩沖液硫酸軟骨素自制片/pH6.8醋酸鹽緩沖液硫酸軟骨素片市售品/pH6.8醋酸鹽緩沖液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硫酸軟骨素片在水中溶出曲線(xiàn)1202308060402000

市售品自制片20406080

硫酸軟骨素片在pH1.0HCl中溶出曲線(xiàn)120230806040200020406080市售品自制片

硫酸軟骨素片在pH4.0醋酸鹽緩沖液中溶出曲線(xiàn)140120230806040200020406080市售自制硫酸軟骨素片在pH6.8磷酸鹽緩沖液中溶出曲線(xiàn)1202308060402000

表3硫酸軟骨素片與上市品溶出曲線(xiàn)相像因子比較溶出介質(zhì)F2水66.580.1mol/l鹽酸51.19pH4.076.08PH6.861.07市售自制20406080三、硫酸軟骨素膠囊回收率結(jié)果見(jiàn)下表：

表4硫酸軟骨素膠囊回收率溶出介質(zhì)原料參與量/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鹽酸70%38.813939.05100%54.7955.0455.28130%71.6471.6971.79PH4.0醋酸鹽緩沖液70%38.3638.3438.5100%55.4155.956.24130%71.5371.6971.76PH6.8磷70%38.21A測(cè)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

酸鹽緩沖液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總結(jié)：膠囊回收率在pH1.0鹽酸和pH4.0緩沖鹽中回收率結(jié)果不理想，重復(fù)試驗(yàn)結(jié)果同樣，原因有待查明。

同時(shí)溶出曲線(xiàn)對(duì)比研究試驗(yàn)正在進(jìn)行中。

四、用CPC法測(cè)定方法學(xué)

測(cè)定方法：

滴定液：取2.0g的一水合十六烷基氯化吡啶，縝密稱(chēng)定，置1000ml量瓶，用水溶解并稀釋至刻度，用前超聲波脫氣。

供試品溶液：取硫酸軟骨素鈉片樣品研細(xì)，稱(chēng)取適量，用溶出介質(zhì)溶解并稀釋制成濃度約為0.22mg/ml的溶液，同法制備兩份。

對(duì)照品溶液同法制備。C.測(cè)定

?縝密量取兩份對(duì)照品溶液分別置兩只錐形瓶，每份40ml。?縝密量取每份供試品溶液40ml，分別置兩只錐形瓶中。

?在磁力攪拌下，用滴定液分別滴定，溶液逐漸變渾濁，當(dāng)溶液變澄清并

有類(lèi)白色的沉淀懸浮在溶液中時(shí)為終點(diǎn)。

D.計(jì)算公式

P?V1?W0?Z×100%

V0?W1?(100%?h)式中P：硫酸軟骨素含量，%；

V0：對(duì)照品溶液消耗滴定液的體積，ml；V1：供試品溶液消耗滴定液的體積，ml；W0：對(duì)照品的重量，g；W1：供試品的重量，g；

h：供試品的枯燥失重，%；

Z：對(duì)照品的含量。

表6用CPC法測(cè)定硫酸軟骨素片的回收率70%V17.457.497.4510.46水100%10.4810.4913.61130%13.613.675.7570%5.75.7pH1.0鹽酸7.97100%8.038.0910.3130%10.3210.37.0270%pH4.0醋酸鹽緩沖液7.17.0110.1100%10.051013.05130%12.9712.997.270%pH6.8磷酸鹽緩沖液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