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：比較國(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

2、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)的溶出和吸收?，F(xiàn)在市場(chǎng)上羅紅霉素產(chǎn)品比較多，包括不同的劑型，中國(guó)藥典（95年版）未收載羅紅霉素，各生產(chǎn)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應(yīng)，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；C：國(guó)內(nèi)某廠家提供；D：國(guó)外某廠家提供；規(guī)格均是150mg）；羅紅霉素膠囊（E：國(guó)內(nèi)

3、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150mg）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-1221型紫外可見分光光度計(jì)。2方法與結(jié)果    表1七廠家羅紅霉素累積溶出度結(jié)果（%，X±SD，n=6）     廠家    時(shí)間(min)    含量 %    5    10&#

4、160;   20    30    45    60    A1    10.9±5.9    18.2±8.4    29.6±10.9    36.1±12.9   

5、0;51.7±11.8    57.6±10.8    84.62    A2    57.0±5.7    83.5±6.1    92.8±4.3    96.1±3.9    98.7±5.2 

6、   97.0±4.8    94.24    B1    28.1±10.8    37.4±5.5    53.8±1.6    62.5±7.5    74.5±13.0    73.

7、8±2.9    90.18    B2    73.5±9.8    94.7±8.1    103.0±8.2    105.6±2.9    103.3±5.5    104.2±3.5 

8、60;  94.7    C1    0.49±1.6    1.5±1.6    4.5±3.7    6.1±4.1    9.7±4.4    13.0±5.5    94.25 &#

9、160;  C2    38.2±25.1    60.9±29.0    80.7±26.2    93.5±22.0    89.9±22.3    94.7±22.0    100.98    

10、D1    14.3±3.4    19.1±2.4    27.8±2.9    36.7±1.9    45.2±3.9    55.2±1.8    80.55    D2   

11、60;62.4±2.8    79.7±6.4    93.7±3.4    95.5±2.8    96.2±1.7    96.7±5.1    91.57    E1    -1.4±1.0 &

12、#160;  0.59±2.7    4.8±2.6    9.1±4.3    18.7±4.7    25.0±3.8    77.41    E2    1.2±1.2    5.6±

13、3.5    24.6±14.4    39.2±17.6    50.2±14.7    51.9±10.4    90.36    F1    5.6±1.7    8.4±1.9   

14、 11.9±2.3    17.5±3.0    25.8±4.3    32.9±5.1    89.98    F2    18.8±8.5    71.1±21.4    109.7±9.0&#

15、160;   107.2±11.5    98.6±5.7    99.6±3.8    102.44    G1    -0.92±2.3    0.40±3.1    5.5±5.5   

16、0;14.0±4.0    23.7±5.0    35.7±6.9    91.58    G2    18.5±13.5    30.4±22.5    32.1±20.2    33.2±21.9

17、0;   37.1±19.9    36.9±18.7    99.67        表2各樣品的溶出參數(shù)（X±SD，n=6）     參數(shù)    Td    T50    m   

18、60;A1    75.21±25.7    48.72±19.6    0.82±0.1    A2    5.83±0.7    4.83±0.5    0.51±0.3    B1   

19、;                 31.99±7.7    16.95±5.4    0.63±0.3    B2    4.39±0.63    3.60±0.92 

20、   0.77±0.5    C1    4322.22±5036.6    2074.36±2256.5    0.76±0.4    C2    22.09±28.1    12.48±12.7  

21、0; 0.73±0.4    D1    97.22±21.8    56.08±6.3    0.71±0.1    D2    5.35±0.3    4.37±0.7    0.39±0.1&#

22、160;   E1    135.66±34.5    104.322±17.9    1.61±0.6    E2    74.96±36.1    54.37±28.7    1.13±0.4   

23、; F1    284.98±119.9    167.85±60.9    0.72±0.1    F2    6.88±3.6    5.87±2.9    1.10±0.3    G1 

24、0;  114.00±26.9    86.56±15.8    1.41±0.5    G2    8274.86±8542.67    1989.03±2466.67    0.19±0.09    表3不同廠家樣品在同一介質(zhì)中溶出參數(shù)

25、的F檢驗(yàn)（A、B、C、D、E、F、G）     er>p0.05    p0.05    p0.01    p0.01    B與C    p0.05    p0.01    p0.01    p0.05  

26、60; p0.05    p0.05    B與D    p0.05    p0.05    p0.05    p0.05    p0.05    p0.05    B與E    p0.01

27、    p0.05    p0.05    p0.05    p0.05    p0.05    B與F    p0.05    p0.05    p0.05    p0.05  

28、  p0.05    p0.05    B與G    p0.05    p0.05    p0.05    p0.05    p0.01    p0.01    C與D    p0

29、.05    p0.01    p0.01    p0.01    p0.05    p0.05    C與E    p0.01    p0.01    p0.01    p0.05 

30、60;                 p0.05    p0.05    C與F    p0.05    p0.01    p0.01    p0.05   

31、 p0.05    p0.05    C與G    p0.05    p0.01    p0.01    p0.05    p0.01    p0.01    D與E    p0.01

32、60;   p0.05    p0.05    p0.01    p0.05    p0.05    D與F    p0.05    p0.05    p0.05    p0.01  

33、60; p0.05    p0.05    D與G    p0.05    p0.05    p0.05    p0.05    p0.01    p0.01    E與F    p0.01

34、    p0.05    p0.05    p0.05    p0.05    p0.05    E與G    p0.05    p0.05    p0.05    p0.01  

35、  p0.01    p0.01    F與G    p0.01    p0.05    p0.05    p0.01    p0.01    p0.01    1.10±0.3  

36、0; G1    114.00±26.9    86.56±15.8    1.41±0.5    G2    8274.86±8542.67    1989.03±2466.67    0.19±0.09   

37、0;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、C、D、E、F、G）                   p0.05    p0.05    p0.05    A與D    p0.05    p0.05

38、0;   p0.05    p0.05    p0.05    p0.05    A與D    p0.01    p0.05    p0.05    p0.05    p0.05  

39、0; p0.05    A與F    p0.05    p0.05    p0.05    p0.05    p0.05    p0.05    A與G    p0.05    p0.05&

40、#160;   p0.05    p0.05    p0.01    p0.01    B與C    p0.05    p0.01    p0.01    p0.05    p0.05  &

41、#160; p0.05    B與D    p0.05    p0.05    p0.05    p0.05    p0.05    p0.05    B與E    p0.01    p0.

42、05    p0.05    p0.05    p0.05    p0.05    B與F    p0.05    p0.05    p0.05    p0.05    p0.05 

43、0;  p0.05    B與G    p0.05    p0.05    p0.05    p0.05    p0.01    p0.01    C與D    p0.05    

44、p0.01    p0.01    p0.01    p0.05    p0.05    C與E    p0.01    p0.01    p0.01    p0.05    p0.05 &

45、#160;  p0.05    C與F    p0.05    p0.01    p0.01    p0.05    p0.05    p0.05    C與G    p0.05   

46、60;p0.01    p0.01    p0.05    p0.01    p0.01    D與E    p0.01    p0.05    p0.05    p0.01    p0.05

47、0;   p0.05    D與F    p0.05    p0.05    p0.05    p0.01    p0.05    p0.05    D與G    p0.05   

48、 p0.05    p0.05    p0.05    p0.01    p0.01    E與F    p0.01    p0.05    p0.05    p0.05    p0.05&

49、#160;   p0.05    E與G    p0.05    p0.05    p0.05    p0.01    p0.01    p0.01    F與G    p0.01  

50、60; p0.05    p0.05    p0.01    p0.01    p0.01                 C1    4322.22±5036.6    

51、;2074.36±2256.5    0.76±0.4    C2    22.09±28.1    12.48±12.7    0.73±0.4    D1    97.22±21.8    56.08±6.

52、3    0.71±0.1    D2    5.35±0.3    4.37±0.7    0.39±0.1    E1    135.66±34.5    104.322±17.9   

53、 1.61±0.6    E2    74.96±36.1    54.37±28.7    1.13±0.4    F1    284.98±119.9    167.85±60.9    0.72±

54、;0.1    F2    6.88±3.6    5.87±2.9    1.10±0.3    G1    114.00±26.9    86.56±15.8    1.41±0.5   

55、; G2    8274.86±8542.67    1989.03±2466.67    0.19±0.09    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、C、D、E、F、G）     er>p0.05    p0.05    p0.01 

56、0;  p0.01    B與C    p0.05    p0.01    p0.01    p0.05    p0.05    p0.05    B與D    p0.05    

57、p0.05    p0.05    p0.05    p0.05    p0.05    B與E    p0.01    p0.05    p0.05    p0.05    p0.05 &

58、#160;  p0.05    B與F    p0.05    p0.05    p0.05    p0.05    p0.05    p0.05    B與G    p0.05    p0.05    p0.05    p0.05    p0.01    p0.01    C與D    p0.05    p0.01    p0.01    p0.01