跳到主要內容

臺灣博碩士論文加值系統

(44.210.149.205) 您好!臺灣時間:2024/04/16 20:05
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:霍俊達
研究生(外文):Chun-Ta Hou
論文名稱:探討□□類藥物在不同pH值中的溶離速率及機制
論文名稱(外文):Investigate the dissolution rate and mechanism of the quinolone drug in different pH
指導教授:劉振倫劉振倫引用關係
指導教授(外文):Chen-Lun Liu
學位類別:碩士
校院名稱:國立東華大學
系所名稱:生物技術研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:72
相關次數:
  • 被引用被引用:5
  • 點閱點閱:482
  • 評分評分:
  • 下載下載:42
  • 收藏至我的研究室書目清單書目收藏:0
□□類的抗生素因為在臨床上有良好的功效,而被普遍的使用。Nalidixic acid是□□家族的第一個藥物,主要用於治療泌尿系統的感染。過去的數十年間,有很多含氟之□□(fluoroquinolone)衍生物被製作成適當劑型來使用。過去雖然有許多關於fluoroquinolone藥物的文獻,但對於其pH值、旋轉速率及溶離速率等基礎物理化學特性的資料卻十分有限。因此,在本實驗中,我們使用兩種典型的fluoroquinolone 藥物,Norfloxacin及Ciprofloxacin進行關於pH值、旋轉速率及溶離速率對藥物在水溶液中的影響。實驗的方法是採用體外模擬,溶液的pH值從4.5到8.5,溫度為37℃。在Norfloxacin及Ciprofloxacin的實驗中,我們發現溶出速率和旋轉槳轉速有一函數關係。溶離速率(R)和旋轉轉速的平方根(ω1/2)會呈一線性關係。由此,我們能得知此類藥物的溶離機制為擴散控制。另外,我們也發現溶離速率會因pH值的不同而有所不同。在較低的pH值中,也就是酸性的溶液中會比在鹼性的溶液中有較高的溶離速率。
Quinolone antibacterials have been used frequently because of their potency and efficacy clinically. The first drug of quinolone used was Nalidixic acid for treatment of urinary tract infections. In the past decade, many fluoroquinolone agents have been developed or under development to appropriate dose forms.
Although a lot of researches involving fluoroquinolone agents have been reported in the past decades, preformulation results are very limited especially for a detailed correlation between pH, rotating speed and dissolution rate. Moreover, there is no information in the literature of basic physicochemical results recently. Therefore, in this study, we investigated the effect of pH and rotating speed on dissolution rate in the aqueous solution of two typically used quinolones, Norfloxacin and Ciprofloxacin by using in vitro dissolution testing. We measured the dissolution rate of Norfloxacin and Ciprofloxacin over the pH range from 4.5 to 8.5 at temperature 37 0C.
目錄
頁次
中文摘要 ………………………………………………………………i
英文摘要 ……………………………………………………………ii
目錄 …………………………………………………… iv
圖目錄 ………………………………………………………… vi
表目錄 …………………………………………………………ix
第一章 緒論
1.1前言 ………………………………………………………… 1
第二章 文獻回顧
2.1抗微生物藥物分類 ………………………………………………… 4
2.2抗微生物藥物的作用方式 ………………………………………… 5
2.3 Cipfloxacin及Norfloxacin的物理化學性質 …………………… 6
2.4 錠劑中其他的添加劑 …………………………………………… 11
第三章 問題陳述
3.1簡介 …………………………………………………………… 22
3.2藥物產品設計中生物藥劑學的考慮 ………………………………23
3.3溶離體外─體內試驗的相關性 ………………………………… 23
第四章 Norfloxacin的溶出試驗
4.1前言 ……………………………………………………… 25
4.2材料與方法 …………………………………………………………26
4.3結果與討論 …………………………………………………………28
第五章 Ciprofloxacin的溶出試驗
5.1前言 ……………………………………………………… 43
5.2材料與方法 ……………………………………………………… 43
5.3結果與討論 ……………………………………………………… 46
第六章 藥物溶出機制與結果探討
6.1簡介 ……………………………………………………… 57
6.2 Model推導 ……………………………………………………… 57
6.3結果與討論 ……………………………………………………… 62
第七章 結論
7.1總論 ……………………………………………………… 67
參考文獻 ……………………………………………………… 68

圖目錄
頁次
圖2-1抗微生物藥物的作用位置 .……………………………………… 15
圖2-2藥物抑制作用機轉 ……………………………………… 16
圖2-3藥物在脂質膜上的擴散作用 .…………………………………… 17
圖2-4藥物離子化圖示 …………………………………………18
圖2-5 Ciprofloxacin及Norfloxacin的分子結構圖 ……………............. 19
圖4-1小體積靜態錠狀溶出實驗裝置圖 .……………………………… 30
圖4-2小體積靜態錠狀溶出實驗裝置圖 ……………………………… 31
圖4-3 Norfloxacin定量分析(pH=4.5)之檢量線圖 ….……………….…. 32
圖4-4 Norfloxacin定量分析(pH=5.0)之檢量線圖 ….……………….…. 32
圖4-5 Norfloxacin定量分析(pH=5.5)之檢量線圖 ….…………………. 33
圖4-6 Norfloxacin定量分析(pH=6.0)之檢量線圖 ….……………….…. 33
圖4-7 Norfloxacin定量分析(pH=6.5)之檢量線圖 ….……………….. 34
圖4-8 Norfloxacin定量分析(pH=7.0)之檢量線圖 ….……………….…. 34
圖4-9 Norfloxacin定量分析(pH=7.5)之檢量線圖 ….……………….…. 35
圖4-10 Norfloxacin定量分析(pH=8.0)之檢量線圖 ….………………… 35
圖4-11 Norfloxacin定量分析(pH=8.5)之檢量線圖 ….………………… 36
圖4-12 pH=5.0溶液中 Norfloxacin溶出量 ….……………….……….. 37
圖4-13 pH=6.0溶液中 Norfloxacin溶出量 ….……………….……….. 37
圖4-14 pH=7.0溶液中 Norfloxacin溶出量 ….……………….……….. 38
圖4-15 pH=8.0溶液中 Norfloxacin溶出量 ….……………….……….. 38
圖4-16 Norfloxacin在轉速45rpm於不同pH值中的溶離量 …..……39
圖4-17 Norfloxacin溶出與攪拌槳轉速的關係 …….………………39
圖4-18 Norfloxacin 在pH=5.0、5.5及7.5溶離速率和轉速的關係 …. 40
圖4-19 Norfloxacin 在pH=4.5時溶離速率和轉速的關係 ……………. 40
圖4-20 Norfloxacin 在pH=5.0及5.5時溶離速率和轉速的關係 .…. 41
圖4-21 Norfloxacin 在pH=6.0及6.5時溶離速率和轉速的關係 ….. 41
圖4-22 Norfloxacin 在pH=7.0及7.5時溶離速率和轉速的關係 ……. 42
圖4-23 Norfloxacin 在pH=8.0及8.5時溶離速率和轉速的關係 ……. 42
圖5-1小體積靜態錠狀溶出實驗裝置圖 .………………………………. 47
圖5-2 Ciprofloxacin定量分析(pH=4.5)之檢量線圖 ….………….….…. 48
圖5-3 Ciprofloxacin定量分析(pH=5.0)之檢量線圖 ….………….….…. 48
圖5-4 Ciprofloxacin定量分析(pH=5.5)之檢量線圖 ….………….….…. 49
圖5-5 Ciprofloxacin定量分析(pH=6.0)之檢量線圖 ….………….….…. 49
圖5-6 Ciprofloxacin定量分析(pH=7.0)之檢量線圖 ….………….….…. 50
圖5-7 Ciprofloxacin定量分析(pH=7.5)之檢量線圖 ….………….….…. 50
圖5-8 Ciprofloxacin定量分析(pH=8.5)之檢量線圖 ….………….….…. 51
圖5-9 Ciprofloxacin 在pH=4.5時溶離速率和轉速的關係 ………..…. 51
圖5-10 Ciprofloxacin 在pH=5.0及5.5時溶離速率和轉速的關係 .…. 52
圖5-11 Ciprofloxacin 在pH=6.0及7.0時溶離速率和轉速的關係 .…. 52
圖5-12 Ciprofloxacin 在pH=7.5及8.5時溶離速率和轉速的關係 .…. 53
圖5-13 pH=4.5溶液中Ciprofloxacin溶出量 ..….…………….……….. 53
圖5-14 pH=5.0溶液中Ciprofloxacin溶出量 ..….…………….……….. 54
圖5-15 pH=5.5溶液中Ciprofloxacin溶出量 ..….…………….……….. 54
圖5-16 pH=6.0溶液中Ciprofloxacin溶出量 ..….…………….……….. 55
圖5-17 pH=7.0溶液中Ciprofloxacin溶出量 ..….…………….……….. 55
圖5-18 pH=7.5溶液中Ciprofloxacin溶出量 ..….…………….……….. 56
圖5-19 pH=8.5溶液中Ciprofloxacin溶出量 ..….…………….………. 56
圖6-1 Norfloxacin 理論及實驗關係圖(25rpm) …….………………….. 64
圖6-2 Norfloxacin 理論及實驗關係圖(45rpm) …….………………….. 64
圖6-3 Norfloxacin 理論及實驗關係圖(60rpm) …….………………….. 65
圖6-4Ciprofloxacin 理論及實驗關係圖(25rpm) ………………………. 65
圖6-5Ciprofloxacin 理論及實驗關係圖(45rpm) ………………………. 66
圖6-6Ciprofloxacin 理論及實驗關係圖(60rpm) ………………………. 66
表目錄
頁次
表2-1 Quinolone藥物動力學參數 …… 20
表2-2錠劑常用添加劑 ………………… 21
參考文獻
1. 郭雅音,謝素娥,羅雪霞。2000。微生物學。藝軒圖書出版社。台灣。pp: 3-5, 61-63。
2. 何曼德。2001。對台灣抗生素抗藥性的認識。國家衛生研究。6(3)。
3. 陳長安。1997。藥劑學。合記出版社。台灣。pp: 33-40。
4. 田蔚城等。1996。生物產業與製藥產業。九州圖書文物有限公司。台灣,台北。pp : 84-86,171。
5. 劉正雄。1997。應用生物藥劑學與藥物動力學。合記圖書出版社。台北,台灣。pp : 139-149。
6. 李德仁等。2002。溶離試驗儀的回顧與未來展望。科儀新知。23(4),72-92。
7. 溶離與藥物的吸收,賴金星。1989。藥學雜誌。5(4),44-47。
8. Wise R., Andrews J. M., Edwards L. J. 1983. In vitro activity of Bay 09867, a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrobial Agents & Chemotherapy 23 (4): 559-64.
9. Roy C., Foz A., Segura C., Tirado M., Teixell M., Teruel D. 1983. Activity of ciprofloxacin BAYo 9867 against Pseudomonas aeruginosa and ampicillin-resistant Enterobacteriaceae. Infection 11(6): 326-8.
10. Chin N. X., Neu H. C. 1984. Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria. Antimicrobial Agents & Chemotherapy 25(3): 319-26.
11. Zeiler HJ. Grohe K. 1984. The in vitro and in vivo activity of cipro -floxacin. European Journal of Clinical Microbiology 3(4): 339-43.
12. Torniainen K., Askolin C. P., Mattinen J. 1997. Isolation and structure elucidation of an intermediate in the photodegradation of ciproflo -xacin. Journal of Pharmaceutical & Biomedical Analysis 16(3): 439-45.
13. Ross D. L., Riley C. M. 1994. Dissociation and complexation of the fluoroquinolone antimicrobials--an update. Journal of Pharmaceu -tical & Biomedical Analysis 12(10): 1325-31.
14. Barbosa J., Barron D., Jimenez-Lozano E. 1998. Effect of pH and evaluation of ionization constants. Journal of Chromatography A 183-192.
15. Rodriguez C. M., Gonzalez A. I., Sanchez-Navarro A., Sayalero M. L. 1999. In vitro study of the interaction between quinolones and polyvalent cations. Pharmaceutical Acta Helvetiae 73(5): 237-245.
16. Theodore M., Scott C., Surya M., Nivedita P. 2000. Experimental investigation and mathematical modeling of pluronic F127 gel dissolution: drug release in stirred system. Journal of Controlled Release 67: 191-202.
17. Lopez-Solis J., Villafuerte-Robles L. 2001. Effect of disintegrants with different hygroscopicity on dissolution of Norfloxacin/ Pharmatose DCL 11 tablets. International Journal Pharmaceutics 216(1-2): 127-135.
18. Samia M., El-Sadek M., Awad E. A. 2002. Spectrophotometric determination of ciprofloxacin, norfloxacin and pefloxacin through charge transfer complex formation. Journal of Pharmaceutical & Biomedical Analysis (27): 133-142.
19. Dutta P., Beskok A. 2001. Analytical solution of combined electroos -motic pressure driven flows in two—dimensional straight : finite Debye layer. Analytical Chemistry 73(9):1979-1986.
20. Cordoba-Diaz M., Cordoba-borrego M., Cordoba-Diaz D. 1998. Modification of fluorescent properties of norfloxacin in the presence of certain antacids. Journal of Pharmaceutical & Biomedical Analysis 18: 565-571.
21. Abdel F. M., Walily E., Saeid F., Rania S. B. 1996. Spectrophotome -tric and spectrofluorimetric estimation of ciprofloxacin and norflo -xacin by ternary complex formation with eosin and palladium(II). Journal of Pharmaceutical and Biomedical Analysis (14): 561-563.
22. Yoa-pu H., The-Min H., Bor-liang C. 1995. Various measure of rate and extent of absorption in bioequivalent study of norfloxacin tablet. The Chinese Pharmaceutical Journal 47: 363-376.
23. Danna L. R., Christopher M. R. 1992. Physicochemical properties of the fluoroquinolone antimicrobials III. Complexation of lomefloxacin with various metal ions and the effect of metal ion complexation on aqueous solubility. International Journal of Pharmaceutics (87): 203-213.
24. Ronald C. L., David E. N., Jerome J. S. 1994. Interaction between ciprofloxacin and metal cations: Its influence on physicochemical characteristics and antibacterial activity. Pharmaceutical Research 11: 917-902.
25. Anargiros I. D., Pinelopi C. I. 1997. Spectrofluorimetric study of the acid-base equilibria and complexation behavior of the fluoro -quinolone antibiotics ofloxain, norfloxacin, ciprofloxacin and pefloxacin in aqueous solution. Analytical Chimica Acta (354): 197-204.
26. Palecz B., Piekarski H. 1999. Dissolution enthalpy of glycine in aqueous solution of bivalent metal electrolytes. Fluid Phase Equilibria 164(1999): 257-265.
27. Yu X., Zipp G., Davidson G. W. 1994. The effect of temperature and pH on the solubility of quinolone compounds: estimation of heat of fusion. Pharmaceutical Research 11(4): 522-527.
28. Saesmaa T., Totterman A. M. 1990. Dissolution studies on ampicillin embonate and amoxicillin embonate. Journal of Pharmaceutical & Biomedical Analysis 8(1): 61-5.
29. Riley C. M., Ross D. L., Vander D., Takusagawa F. 1993. Characteri -zation of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy. Journal of Pharmaceutical & Biomedical Analysis 11(1): 49-59.
30. Tsuji A., Nakashima M., Hamano S., Yamana T. 1977. Physicochem -ical properties of amphoteric β-Lactam antibiotics I: stability, solution, and dissolution behavior of amino penicillins as a function of pH. Journal of Pharmaceutical Sciences (67): 1059-1066.
31. Bettini R., Catellani P. L., Sani P., Massimo G., Peppas N. A., Colombo P. 2001. Translocation of drug particles in HPMC matrix gel layer: Effect of drug solubility and influence on release rate. Journal of Controlled Release 70: 383-391.
32. Hopkala H., Kowalczuk D. 2000. Application of derivative UV spectrophotometry for the determination of ciprofloxacin, norfloxacin and ofloxacin in tablets. Acta Poloniae Pharmaceutica 57(1): 3-13.
33. Schonfeld W., Knoller J., Bremm K. D., Dahlhoff A., Weber B., Konig W. 1986. Determination of ciprofloxacin, norfloxacin and ofloxacin by high performance liquid chromatography. Parasitology 261(3): 338-344.
34. John S. G., Keith E. A., James A. R., Robert T. F. 1997. Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. I: Description of a two-phase in vitro dissolution test. Journal of Controlled Release 48:1-8.
35. Dong-Sun L., Hee-jung H., Kun K., Won-Bong P., Jung-Kil C., Jae-Hyun K. 1994.Dissociation and complexation of fluoroquino -lone analogues. Journal of Pharmaceutical & Biomedical Analysis (12): 157-164.
36. Borrego C., Diaz M. C., Martin M. R., Cienfuegos A., Rodriguez J. M. 1995. Validation of a method to study the dissolution behavior of norfloxacin tablets. Pharmaceutica Acta Helvetiae 70(4): 339-342.
37. Cordoba-Borrego M., Cordoba-Diaz M., Bernabe I., Cordoba-Diaz D. 1995. Determination of norfloxacin by fluorescence in the presence of different antacids: quantification of analytical interferences. Journal of Pharmaceutical and Biomedical Analysis 41: 977-982.
38. Lorena F., Elfrides E. S. 1995. Ciprofloxacin determination by visible light spectrophotometry using iron (III) nitrate. International Journal of Pharmaceutics 127: 279-282.
39. Tsuji A., Nakashima E., Yamana T. 1979. Physicochemical properties of amphoteric beta-lactam antibiotics. II: Solubility and dissolution behavior of aminocephalosporins as a function of pH. Journal of Pharmaceutical Sciences 68(3): 308 -11.
40. Miic C. 1988. A quantitative theory of the stern electric double layer. Electrophoresis 9(4): 201-202.
41. Higuchi W. I., Parrott E. L., Wurster D. E., Higuchi T. 1958. Investi -gation of drug release from solids II. J. Am. Pharm. Asso., Sci. Ed. 47: 376-383.
42. John M. P., Kellaway I. W. 1975. The diffusion of penicillin G and ampicillin through phospholipids sols. J. Pharm. Pharmac 27: 348-352.
43. Stokes R. H. 1950. The diffusion coefficients of eight Uni-univalent Electrolytes in aqueous solution at 25℃. J. Am. Chem. Soc. 72: 2243 -2247.
44. Bhatia R. N., Gubbins K. E., Walker R. D. 1968. Mutual diffusion in concentrated aqueous potassium hydroxide solutions. Trans. Faraday Soc. 64: 2091-2009.
45. Hisashi N., Tsuneji N., Akira S. 1966. Dissolution rate of sulfona -mides by rotating disk method. Chem. Pharm. Bull 14(4):329-338.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top