國(guó)內(nèi)外七廠家羅紅霉素在兩種介質(zhì)中的溶出度考察

1、國(guó)內(nèi)外七廠家羅紅霉素在兩種介質(zhì)中的溶出度考察摘要目的：比擬國(guó)內(nèi)外7廠家羅紅霉素在兩種介質(zhì)中的體外溶出度。方法：采用紫外分光光度法測(cè)定7廠家羅紅霉素的含量和在兩種不同介質(zhì)中的溶出度。結(jié)果：7廠家羅紅霉素在人工胃液中溶出度均不符合要求，在人工腸液中有2家產(chǎn)品不符合要求。結(jié)論：羅紅霉素在兩種介質(zhì)中溶出度有很大差異，各廠家之同的產(chǎn)品溶出度也存在差異，選用羅紅霉素時(shí)注意產(chǎn)品質(zhì)量。關(guān)鍵詞：羅紅霉素溶出度介質(zhì)固體口服制劑的溶出度是控制藥品質(zhì)量、有效保證體內(nèi)生物利用度的重要指標(biāo)。羅紅霉素是新型大壞內(nèi)酯類抗生素，與紅霉素有相似抗菌譜，藥物動(dòng)力學(xué)優(yōu)于紅霉素。由于羅紅霉素具強(qiáng)疏水性，制劑工藝將影響其在體內(nèi)的溶出和吸

2、收。如今市場(chǎng)上羅紅霉素產(chǎn)品比擬多，包括不同的劑型，中國(guó)藥典95年版未收載羅紅霉素，各消費(fèi)廠家測(cè)定溶出度時(shí)均采用地方標(biāo)準(zhǔn)，溶出介質(zhì)不同，為此我們對(duì)國(guó)內(nèi)外7廠家羅紅霉素在兩種介質(zhì)中溶出度迸行了考察。我們利用硫酸呈色反響，采用比色法測(cè)定羅紅霉素的溶出量。1實(shí)驗(yàn)材料和儀器1.1試樣與拭劑羅紅霉素對(duì)照品效價(jià)970u；羅紅霉素片劑A：香港某廠家提供；B：國(guó)內(nèi)某廠家提供；：國(guó)內(nèi)某廠家提供；D：國(guó)外某廠家提供；規(guī)格均是150g；羅紅霉素膠囊E：國(guó)內(nèi)某廠家提供；F：國(guó)內(nèi)某廠家提供1；G：國(guó)內(nèi)某廠家提供，規(guī)格均是150g試劑均為分析純。1.2儀器天津無(wú)線電廠ZRS-4智能溶出試驗(yàn)儀，北京市通用儀器設(shè)備公司TU-1

3、221型紫外可見(jiàn)分光光度計(jì)。2方法與結(jié)果2.1標(biāo)準(zhǔn)曲線的制備2.1.1以胃液為溶出介質(zhì)精細(xì)稱取羅紅霉素對(duì)照品適量，加適量乙醇溶解后，加鹽酸91000制成每1l含200u的溶液。再精細(xì)量取該溶液.5，1.，1.3，2.，2.5，3.置具塞拭管中，分別補(bǔ)充鹽酸910005l，搖勻，加硫酸溶液751005l，搖勻，自然冷卻30in。另取鹽酸910005l依法作空白，于482n波長(zhǎng)處測(cè)定吸收度，以吸收度對(duì)硫酸顯色后濃度計(jì)算回歸方程：A.0207.188r.9992.1.2以腸液為溶出介質(zhì)操作內(nèi)容同上，只是將鹽酸91000換成磷酸鹽緩沖液PH=6.8?；貧w方程：A.0183十.0043r.9992.2含

4、量測(cè)定分別取A、B、D、B、F、G各10片粒，精細(xì)稱定膠囊去掉外殼，研細(xì)，精細(xì)稱取適量約相當(dāng)于羅紅霉素150g，溶解定容至100l，濾過(guò)，取續(xù)濾液10.l定容至100l，在482n波長(zhǎng)處測(cè)定吸收度，分別按各自相對(duì)應(yīng)的回歸方程計(jì)算其含量。2.3溶出曲線的繪制分別取A、B、D、E、F、G各10片粒，照溶出度測(cè)定法第二法，以鹽酸91000或磷酸鹽緩沖液PH=6.8900l溶劑，轉(zhuǎn)速為50r/in，溫度恒定力37.5，依法測(cè)定，分別于5、10、20、30、45、60in時(shí)定點(diǎn)取樣5l同時(shí)立即補(bǔ)充釋放介質(zhì)5l，濾過(guò)，精細(xì)量取續(xù)濾液2.l置具塞試管中，加介質(zhì)3.0l，搖勻，自然冷卻30in。另取介質(zhì)5.l

5、依法作空白，于482n波長(zhǎng)處測(cè)定吸收度，分別按各自相對(duì)應(yīng)的回歸方程計(jì)算出各時(shí)間羅紅霉素的平均積累積溶出百分率表1。表1七廠家羅紅霉素累積溶出度結(jié)果%，XSD，n=6廠家時(shí)間(in)含量%51020304560A110.95.918.28.429.610.936.112.951.711.857.610.884.62A257.05.783.56.192.84.396.13.998.75.297.04.894.24B128.110.837.45.553.81.662.57.574.513.073.82.990.18B273.59.894.78.1103.08.2105.62.9103.35.5104

6、.23.594.710.491.61.51.64.53.76.14.19.74.413.05.594.25238.225.160.929.080.726.293.522.089.922.394.722.0100.98D114.33.419.12.427.82.936.71.945.23.955.21.880.55D262.42.879.76.493.73.495.52.896.21.796.75.191.57E1-1.41.00.592.74.82.69.14.318.74.725.03.877.41E21.21.25.63.524.614.439.217.650.214.751.910.49

7、0.36F15.61.78.41.911.92.317.53.025.84.332.95.189.98F218.88.571.121.4109.79.0107.211.598.65.799.63.8102.44G1-0.922.30.403.15.55.514.04.023.75.035.76.991.58G218.513.530.422.532.120.233.221.937.119.936.918.799.67表2各樣品的溶出參數(shù)XSD，n=6參數(shù)TdT50A175.2125.748.7219.60.820.1A25.830.74.830.50.510.3B131.997.716.955.

8、40.630.3B24.390.633.600.920.770.514322.225036.62074.362256.50.760.4222.0928.112.4812.70.730.4D197.2221.856.086.30.710.1D25.350.34.370.70.390.1E1135.6634.5104.32217.91.610.6E274.9636.154.3728.71.130.4F1284.98119.9167.8560.90.720.1F26.883.65.872.91.100.3G1114.0026.986.5615.81.410.5G28274.868542.671989

9、.032466.670.190.09表3不同廠家樣品在同一介質(zhì)中溶出參數(shù)的F檢驗(yàn)A、B、D、E、F、G參數(shù)F值胃P胃F值腸P腸TdT504.1784.7017.1410.010.010.019.8185.5143.9480.010.010.01表4同一廠家樣品在不同溶出介質(zhì)中溶出t檢驗(yàn)P值參數(shù)TdT500.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05表5不同廠家樣品在同一介質(zhì)中溶出參數(shù)的q檢驗(yàn)(A、B、E、D、F、G)胃胃Td胃T50腸腸Td腸T50A與Bp0.05p0.05

10、p0.05p0.05p0.05p0.05A與p0.05p0.01p0.01p0.05p0.05p0.05A與Dp0.05p0.05p0.05p0.05p0.05p0.05A與Dp0.01p0.05p0.05p0.05p0.05p0.05A與Fp0.05p0.05p0.05p0.05p0.05p0.05A與Gp0.05p0.05p0.05p0.05p0.01p0.01B與p0.05p0.01p0.01p0.05p0.05p0.05B與Dp0.05p0.05p0.05p0.05p0.05p0.05B與Ep0.01p0.05p0.05p0.05p0.05p0.05B與Fp0.05p0.05p0.05

11、p0.05p0.05p0.05B與Gp0.05p0.05p0.05p0.05p0.01p0.01與Dp0.05p0.01p0.01p0.01p0.05p0.05與Ep0.01p0.01p0.01p0.05p0.05p0.05與Fp0.05p0.01p0.01p0.05p0.05p0.05與Gp0.05p0.01p0.01p0.05p0.01p0.01D與Ep0.01p0.05p0.05p0.01p0.05p0.05D與Fp0.05p0.05p0.05p0.01p0.05p0.05D與Gp0.05p0.05p0.05p0.05p0.01p0.01E與Fp0.01p0.05p0.05p0.05p0.05p0.05E與Gp0.05p0.05p0.05p0.01p0.01p0.01F與Gp0.01p0.05p0.05p0.01p0.01p0.012.4提取參數(shù)根據(jù)Eibull分布模型，計(jì)算出Td、T50、等溶出參數(shù)表2，對(duì)其刊行統(tǒng)計(jì)處理，結(jié)果見(jiàn)表3、表4、表5。3討論3.1假如參照中國(guó)藥典對(duì)大局部片劑溶出量的一般限度45in時(shí)的溶出量不低于標(biāo)示量的75，從表1中可以看