国内外七厂家罗红霉素在两种介质中的溶出度考察

1、国内外七厂家罗红霉素在两种介质中的溶出度考察摘要目的：比拟国内外7厂家罗红霉素在两种介质中的体外溶出度。方法：采用紫外分光光度法测定7厂家罗红霉素的含量和在两种不同介质中的溶出度。结果：7厂家罗红霉素在人工胃液中溶出度均不符合要求，在人工肠液中有2家产品不符合要求。结论：罗红霉素在两种介质中溶出度有很大差异，各厂家之同的产品溶出度也存在差异，选用罗红霉素时注意产品质量。关键词：罗红霉素溶出度介质固体口服制剂的溶出度是控制药品质量、有效保证体内生物利用度的重要指标。罗红霉素是新型大坏内酯类抗生素，与红霉素有相似抗菌谱，药物动力学优于红霉素。由于罗红霉素具强疏水性，制剂工艺将影响其在体内的溶出和吸

2、收。如今市场上罗红霉素产品比拟多，包括不同的剂型，中国药典95年版未收载罗红霉素，各消费厂家测定溶出度时均采用地方标准，溶出介质不同，为此我们对国内外7厂家罗红霉素在两种介质中溶出度迸行了考察。我们利用硫酸呈色反响，采用比色法测定罗红霉素的溶出量。1实验材料和仪器1.1试样与拭剂罗红霉素对照品效价970u；罗红霉素片剂A：香港某厂家提供；B：国内某厂家提供；：国内某厂家提供；D：国外某厂家提供；规格均是150g；罗红霉素胶囊E：国内某厂家提供；F：国内某厂家提供1；G：国内某厂家提供，规格均是150g试剂均为分析纯。1.2仪器天津无线电厂ZRS-4智能溶出试验仪，北京市通用仪器设备公司TU-1

3、221型紫外可见分光光度计。2方法与结果2.1标准曲线的制备2.1.1以胃液为溶出介质精细称取罗红霉素对照品适量，加适量乙醇溶解后，加盐酸91000制成每1l含200u的溶液。再精细量取该溶液.5，1.，1.3，2.，2.5，3.置具塞拭管中，分别补充盐酸910005l，摇匀，加硫酸溶液751005l，摇匀，自然冷却30in。另取盐酸910005l依法作空白，于482n波长处测定吸收度，以吸收度对硫酸显色后浓度计算回归方程：A.0207.188r.9992.1.2以肠液为溶出介质操作内容同上，只是将盐酸91000换成磷酸盐缓冲液PH=6.8。回归方程：A.0183十.0043r.9992.2含

4、量测定分别取A、B、D、B、F、G各10片粒，精细称定胶囊去掉外壳，研细，精细称取适量约相当于罗红霉素150g，溶解定容至100l，滤过，取续滤液10.l定容至100l，在482n波长处测定吸收度，分别按各自相对应的回归方程计算其含量。2.3溶出曲线的绘制分别取A、B、D、E、F、G各10片粒，照溶出度测定法第二法，以盐酸91000或磷酸盐缓冲液PH=6.8900l溶剂，转速为50r/in，温度恒定力37.5，依法测定，分别于5、10、20、30、45、60in时定点取样5l同时立即补充释放介质5l，滤过，精细量取续滤液2.l置具塞试管中，加介质3.0l，摇匀，自然冷却30in。另取介质5.l

5、依法作空白，于482n波长处测定吸收度，分别按各自相对应的回归方程计算出各时间罗红霉素的平均积累积溶出百分率表1。表1七厂家罗红霉素累积溶出度结果%，XSD，n=6厂家时间(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各样品的溶出参数XSD，n=6参数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不同厂家样品在同一介质中溶出参数的F检验A、B、D、E、F、G参数F值胃P胃F值肠P肠TdT504.1784.7017.1410.010.010.019.8185.5143.9480.010.010.01表4同一厂家样品在不同溶出介质中溶出t检验P值参数TdT500.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05表5不同厂家样品在同一介质中溶出参数的q检验(A、B、E、D、F、G)胃胃Td胃T50肠肠Td肠T50A与Bp0.05p0.05

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

11、p0.05p0.05p0.05B与Gp0.05p0.05p0.05p0.05p0.01p0.01与Dp0.05p0.01p0.01p0.01p0.05p0.05与Ep0.01p0.01p0.01p0.05p0.05p0.05与Fp0.05p0.01p0.01p0.05p0.05p0.05与Gp0.05p0.01p0.01p0.05p0.01p0.01D与Ep0.01p0.05p0.05p0.01p0.05p0.05D与Fp0.05p0.05p0.05p0.01p0.05p0.05D与Gp0.05p0.05p0.05p0.05p0.01p0.01E与Fp0.01p0.05p0.05p0.05p0.05p0.05E与Gp0.05p0.05p0.05p0.01p0.01p0.01F与Gp0.01p0.05p0.05p0.01p0.01p0.012.4提取参数根据Eibull分布模型，计算出Td、T50、等溶出参数表2，对其刊行统计处理，结果见表3、表4、表5。3讨论3.1假如参照中国药典对大局部片剂溶出量的一般限度45in时的溶出量不低于标示量的75，从表1中可以看