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研究生:張家銘
研究生(外文):Chia-Ming Chang
論文名稱:利用熔融包覆法製備蘭索拉唑微粒劑型之研究
論文名稱(外文):The study of lansoprazole microparticles prepared by hot melt microencapsulation method
指導教授:林文貞
指導教授(外文):Wen-Jen Lin
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:154
中文關鍵詞:蘭索拉唑熔融包覆法微粒
外文關鍵詞:LansoprazoleHot melt microencapsulationMicroparticles
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安定性對藥物產品是否能成功開發具有指標性的作用,如果藥物受到降解,它不只會使療效下降,可能還會生成有害的降解產物。因此對藥物安定性、降解的機制及模式等研究日受重視。在本研究中,以蘭索拉唑(Lansoprazole)為一模式藥物,對其安定性進行研究。此外,利用生分解性材料製備可緩釋藥物的微球載體,是近年來廣泛被研究的主題,本實驗選用生分解性聚合物聚己內酯(Poly-ε-caprolactone, PCL)作為包覆藥物的材料,利用熔融包覆法製作微球,可避免有機溶劑的使用。
實驗中對蘭索拉唑安定性的研究分成兩個部份,分別是以聚乙二醇300及聚乙烯醇水溶液為外相,於70℃加熱觀察藥物經時變化。若以聚乙二醇300為外相,則探討蘭索拉唑/聚乙二醇300重量比及聚己內酯對蘭索拉唑的影響;而以聚乙烯醇水溶液為外相,則探討蘭索拉唑在聚己內酯、聚乙烯醇水溶液、聚己內酯+聚乙烯醇水溶液中的安定性。接著利用熔融包覆法將蘭索拉唑包覆於聚己內酯微球中,並控制製作過程中聚乙烯醇濃度、藥物/聚合物重量比及超音波打碎時間等變因,對微球進行評估。
實驗結果顯示,不同蘭索拉唑/聚乙二醇300重量比,於70℃的藥物降解速率為1/1000組別 > 10/1000組別 > 100/1000組別,其降解最適合以零階動力模式描述;相較於聚己內酯,蘭索拉唑較易存留在聚乙二醇300中,且安定性也較在聚己內酯中佳。蘭索拉唑在聚己內酯及聚乙烯醇水溶液不同組合下,於70℃的藥物降解速率為(蘭索拉唑+聚己內酯+聚乙烯醇)組別 > (蘭索拉唑+聚己內酯)組別 > (蘭索拉唑+聚乙烯醇)組別 > 蘭索拉唑組別,其降解最適合以一階動力模式描述。在HPLC層析圖譜中最多可觀察到6個降解物生成,以RT (Retention time)13.3分鐘降解物生成最快且最多。
在蘭索拉唑-聚己內酯微球的研究方面,以熔融包覆法所製得微球產率皆有80%以上;藥品包覆率及藥品含量會隨著藥物/聚合物重量比的增加而增加,但隨著超音波打碎時間的增加而減少;在SEM觀察下,可看到微球具有球狀外觀,唯表面較為粗糙,微球粒徑分佈寬廣顆粒大小摻雜。經FT-IR及DSC分析可知,蘭索拉唑是以物理性包覆於聚己內酯,且其結晶度會受聚己內酯的影響。在體外溶離試驗中,經f1值與f2值分析可得知,聚乙烯醇濃度及藥物/聚合物重量比對微球的釋離結果並無明顯差別;而以超音波打碎時間3分鐘的藥物釋離速度及累積釋離量明顯最快且最高。在腸衣包覆試驗結果顯示,聚己內酯微球有減緩酸降解蘭索拉唑的能力,而經腸衣包覆之微球膠囊則可完全保護蘭索拉唑免於被酸降解,且藥物釋離結果不受影響。
在大鼠體內藥物動力學的結果顯示,相較於靜脈注射蘭索拉唑溶液,口服微球的半衰期(T1/2)及平均滯留時間(MRT)較長,因此可延長藥物的作用時間。唯微球的生體可用率僅3.4%,顯示此微球劑型要應用於活體內,需再包覆一層腸溶膜衣。


摘 要 I
英文摘要 III
目 錄 V
圖目錄 XI
表目錄 XVII
第一章 緒論 1
一、微膠囊生分解性材料 1
二、微粒膠囊化法 2
三、緩控釋製劑 7
四、質子幫浦抑制劑簡介 11
五、藥品安定性 16
第二章 材料與試劑介紹 20
一、聚己內酯 (Poly-ε-caprolactone, PCL) 20
二、蘭索拉唑 (lansoprazole) 21
三、聚乙烯醇 (polyvinyl alcohol, PVA) 25
四、聚乙二醇300 (Polyethylene glycol 300, PEG 300) 27
五、聚山梨酯80 (Polysorbate 80, Tween 80) 28
六、Eudragit® L100-55 29
第三章 實驗動機與目的 30
第四章 實驗試劑與儀器 31
一、試劑 31
二、儀器 32
三、耗材 34
四、藥品溶液及緩衝液之配製 35
五、體內試驗用動物 36
第五章 實驗方法 37
一、蘭索拉唑的安定性研究 37
(一)實驗設計 37
(二)製作方式 37
(三)計算藥物殘留百分比 44
(四)安定性試驗數據的處理 44
(五)降解物的消長 45
(六)顏色觀察 45
(七)pH值 45
二、蘭索拉唑定量方法 46
(一)建立標準曲線 46
(二)分析方法的確效 47
三、蘭索拉唑-聚己內酯微球的製備 48
(一)製作方式 48
(二)控制變因 50
四、蘭索拉唑-聚己內酯微球的物性分析 51
(一)產率 51
(二)藥品含量 51
(三)藥品包覆率 51
(四)粒徑分析 52
(五)型態觀察 52
(六)傅立葉轉換紅外線光譜儀 52
(七)示差掃描熱分析儀 53
(八)統計方法 54
五、 體外溶離試驗 55
(一)溶離槽的裝置 55
(二)溶離試驗數據的處理 55
六、腸衣包覆試驗 58
(一)腸衣包覆方法 58
(二)酸安定性試驗 58
(三)腸衣包覆之微球膠囊的溶離試驗 60
(四)微球及腸衣包覆之微球膠囊在pH 7.4磷酸緩衝液的溶離試驗 61
七、微球劑型於動物體內(in vivo)的藥物動力學試驗 61
(一)藥物動力學實驗 61
(二)血漿中蘭索拉唑的定量方法 62
(三)數據分析 63
第六章 實驗結果 65
一、蘭索拉唑的安定性研究 65
(一)以聚乙二醇300為外相 65
(二)以聚乙烯醇水溶液為外相 71
(三)比較蘭索拉唑在聚乙二醇300及聚乙烯醇水溶液的安定性 83
二、蘭索拉唑定量精確度試驗結果 85
三、蘭索拉唑-聚己內酯微球物性分析結果 91
(一)產率 91
(二)藥品包覆率 93
(三)藥品含量 96
(四)粒徑分析 98
(五)微球的外觀型態 103
(六)傅立葉轉換紅外線光譜儀測定 106
(七)示差掃描熱分析儀測定 109
四、蘭索拉唑-聚己內酯微球體外溶離試驗 111
五、腸衣包覆試驗結果 119
(一)酸安定性試驗 119
(二)腸衣包覆之微球膠囊的溶離試驗 121
(三)微球及腸衣包覆之微球膠囊在pH 7.4磷酸緩衝液的溶離試驗 122
六、微球劑型於動物體內(in vivo)的藥物動力學試驗 126
(一)蘭索拉唑血漿中定量精確度試驗結果 126
(二)藥物溶液與微球劑型在血漿中的藥物動力學 130
第七章 討論 132
一、蘭索拉唑的安定性研究 132
(一)以聚乙二醇300為外相 134
(二)以聚乙烯醇水溶液為外相 135
(三)比較蘭索拉唑在聚乙二醇300及聚乙烯醇水溶液的安定性 137
二、蘭索拉唑-聚己內酯微球物性分析結果 138
(一)產率 138
(二)藥品包覆率 138
(三)藥品含量 139
(四)粒徑分析 139
(五)蘭索拉唑-聚己內酯微球的外觀型態 141
(六)傅立葉轉換紅外線光譜儀測定 141
(七)示差掃描熱分析儀測定 142
三、蘭索拉唑-聚己內酯微球體外溶離試驗 143
四、酸安定性試驗 144
五、微球劑型於動物體內(in vivo)的藥物動力學試驗 145
第八章 結論 147
第九章 參考文獻 149

Allen, L. V., Jr. (2008). Dosage form design and development. Clin Ther, 30(11), 2102-2111.
Anderson, L. C., Wise, D. L., & Howes, J. F. (1976). Injectable Sustained-Release Fertility Control-System. Contraception, 13(3), 375-384.
Arifin, D. Y., Lee, L. Y., & Wang, C. H. (2006). Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems. Adv Drug Deliv Rev, 58(12-13), 1274-1325.
Arimori, K., Yasuda, K., Katsuki, H., & Nakano, M. (1998). Pharmacokinetic differences between lansoprazole enantiomers in rats. Journal of Pharmacy and Pharmacology, 50(11), 1241-1245.
Bardou, M., Martin, J., & Barkun, A. (2009). Intravenous Proton Pump Inhibitors An Evidence-Based Review of Their Use in Gastrointestinal Disorders. Drugs, 69(4), 435-448.
Benita, S. (1996). Microencapsulation-Methods and Industrial Application., Marcel Dekker Inc., New York, 1-19,35-72.
Bernardi, L. S., Oliveira, P. R., Murakami, F. S., Borgmann, S. H., Arend, M. Z., & Cardoso, S. G. (2009). Development and validation of a stability-indicating LC method for the determination of venlafaxine in extended-release capsules and dissolution kinetic studies. J Chromatogr Sci, 47(9), 770-776.
Besancon, M., Simon, A., Sachs, G., & Shin, J. M. (1997). Sites of reaction of the gastric H,K-ATPase with extracytoplasmic thiol reagents. J Biol Chem, 272(36), 22438-22446.
Bilati, U., Allemann, E., & Doelker, E. (2005). Poly(D,L-lactide-co-glycolide) protein-loaded nanoparticles prepared by the double emulsion method--processing and formulation issues for enhanced entrapment efficiency. J Microencapsul, 22(2), 205-214.
Costa, P., Manuel, J., & Lobo, S. (2001). Modeling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences, 13(2), 123-133.
Darney, P. D. (1994). The Role of Hormonal Contraceptives: Hormonal Implants: Contraception for a New Century. [Miscellaneous]. Am J Obstet Gynecol, 170(5 pt 2), 1536-1543.
DellaGreca, M., Iesce, M. R., Previtera, L., Rubino, M., Temussi, F., & Brigante, M. (2006). Degradation of lansoprazole and omeprazole in the aquatic environment. Chemosphere, 63(7), 1087-1093.
Demetzos, C. (2008). Differential Scanning Calorimetry (DSC): a tool to study the thermal behavior of lipid bilayers and liposomal stability. J Liposome Res, 18(3), 159-173.
Der, G. (2003). An overview of proton pump inhibitors. Gastroenterol Nurs, 26(5), 182-190.
Desta, Z., Zhao, X., Shin, J. G., & Flockhart, D. A. (2002). Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet, 41(12), 913-958.
DiGiacinto, J. L., Olsen, K. M., Bergman, K. L., & Hoie, E. B. (2000). Stability of suspension formulations of lansoprazole and omeprazole stored in amber-colored plastic oral syringes. Ann Pharmacother, 34(5), 600-605.
Edlund, U., & Albertsson, A. C. (2002). Degradable polymer microspheres for controlled drug delivery. Degradable Aliphatic Polyesters, 157, 67-112.
Gerloff, J., Mignot, A., Barth, H., & Heintze, K. (1996). Pharmacokinetics and absolute bioavailability of lansoprazole. Eur J Clin Pharmacol, 50(4), 293-297.
Gibaldi, M., & Donald, P. (1982). Noncompartmental analysis based on statistical moment theory. New York: Marcel Dekker Inc.
Gremse, D. A. (2001). Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses. Expert Opin Pharmacother, 2(10), 1663-1670.
Higuchi, T. (1963). Mechanism of Sustained-Action Medication - Theoretical Analysis of Rate of Release of Solid Drugs Dispersed in Solid Matrices. Journal of Pharmaceutical Sciences, 52(12), 1145-1149.
Horn, J. R., & Howden, C. W. (2005). Review article: similarities and differences among delayed-release proton-pump inhibitor formulations. [Article]. Alimentary Pharmacology & Therapeutics, 22, 20-24.
Ito, Y., Arai, H., Uchino, K., Iwasaki, K., Shibata, N., & Takada, K. (2005). Effect of adsorbents on the absorption of lansoprazole with surfactant. Int J Pharm, 289(1-2), 69-77.
Jameela, S. R., Suma, N., & Jayakrishnan, A. (1997). Protein release from poly(epsilon-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: a comparative study. J Biomater Sci Polym Ed, 8(6), 457-466.
Katashima, M., Yamamoto, K., Sugiura, M., Sawada, Y., & Iga, T. (1995). Comparative pharmacokinetic/pharmacodynamic study of proton pump inhibitors, omeprazole and lansoprazole in rats. Drug Metab Dispos, 23(7), 718-723.
Khan, M. Z. I., Stedul, H. P., & Kurjakovic, N. (2000). A pH-dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. II. Manipulation of drug release using Eudragit (R) L100 and Eudragit S100 combinations. Drug Dev Ind Pharm, 26(5), 549-554.
Kristl, A. (2009). Acido-basic properties of proton pump inhibitors in aqueous solutions. Drug Dev Ind Pharm, 35(1), 114-117.
Kristl, A., & Vrecer, F. (2000). Preformulation investigation of the novel proton pump inhibitor lansoprazole. Drug Dev Ind Pharm, 26(7), 781-783.
Lee, S. C., Oh, J. T., Jang, M. H., & Chung, S. I. (1999). Quantitative analysis of polyvinyl alcohol on the surface of poly(,-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration. Journal of Controlled Release, 59(2), 123-132.
Lee, W. C., & Chu, I. M. (2008). Preparation and degradation behavior of polyanhydrides nanoparticles. J Biomed Mater Res B Appl Biomater, 84(1), 138-146.
Lemoine, D., Francois, C., Kedzierewicz, F., Preat, V., Hoffman, M., & Maincent, P. (1996). Stability study of nanoparticles of poly(epsilon-caprolactone), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide). Biomaterials, 17(22), 2191-2197.
Li, M. G., Lu, W. L., Wang, J. C., Zhang, X., Zhang, H., Wang, X. Q., et al. (2006). Preparation and characterization of insulin nanoparticles employing chitosan and poly(methylmethacrylate/methylmethacrylic acid) copolymer. Journal of Nanoscience and Nanotechnology, 6(9-10), 2874-2886.
Liao, L. Q., Liu, L. J., Zhang, C., He, F., Zhuo, R. X., & Wan, K. (2002). Microwave-assisted ring-opening polymerization of epsilon-caprolactone. Journal of Polymer Science Part a-Polymer Chemistry, 40(11), 1749-1755.
Lin, W. J., & Kang, W. W. (2003). Comparison of chitosan and gelatin coated microparticles: prepared by hot-melt method. J Microencapsul, 20(2), 169-177.
Lin, W. J., & Yu, C. C. (2001). Comparison of protein loaded poly(epsilon-caprolactone) microparticles prepared by the hot-melt technique. J Microencapsul, 18(5), 585-592.
Lin, Y. K., & Ho, H. O. (2003). Investigations on the drug releasing mechanism from an asymmetric membrane-coated capsule with an in situ formed delivery orifice. J Control Release, 89(1), 57-69.
Matheson, A. J., & Jarvis, B. (2001). Lansoprazole: an update of its place in the management of acid-related disorders. Drugs, 61(12), 1801-1833.
Mehta, K. A., Kislalioglu, M. S., Phuapradit, W., Malick, A. W., & Shah, N. H. (2001). Release performance of a poorly soluble drug from a novel, Eudragit-based multi-unit erosion matrix. Int J Pharm, 213(1-2), 7-12.
Missaghi, S., Young, C., Fegely, K., & Rajabi-Siahboomi, A. R. (2010). Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies. Drug Dev Ind Pharm, 36(2), 180-189.
Miura, M., Tada, H., Yasui-Furukori, N., Uno, T., Sugawara, K., Tateishi, T., et al. (2004). Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes. [10.1007/s00228-004-0809-1]. European Journal of Clinical Pharmacology, 60(9), 623-628.
Moore, J. W., & Flanner, H. H. (1996). Mathematical comparison of dissolution profiles. Pharmaceutical technology 20(6), 64-74.
Nahata, M. C., & Allen, L. V., Jr. (2008). Extemporaneous drug formulations. Clin Ther, 30(11), 2112-2119.
Neppiras, E. A. (1980). Acoustic cavitation. Phys. Rep., 61, 159-251.
Noubarani, M., Keyhanfar, F., Motevalian, M., & Mahmoudian, M. (2010). Improved HPLC Method for Determination of Four PPIs, Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole in Human Plasma. Journal of Pharmacy and Pharmaceutical Sciences, 13(1), 1-10.
Olbe, L., Carlsson, E., & Lindberg, P. (2003). A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov, 2(2), 132-139.
Ory, S. J., Hammond, C. B., Yancy, S. G., Hendren, R. W., & Pitt, C. G. (1983). The effect of a biodegradable contraceptive capsule (Capronor) containing levonorgestrel on gonadotropin, estrogen, and progesterone levels. Am J Obstet Gynecol, 145(5), 600-605.
Pisegna, J. R. (2002). Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition. Crit Care Med, 30(6 Suppl), S356-361.
Pitt, C. G. (1990). Biodegradable Polymers as Drug Delivery System. New York: Marcel Dekker.
Raffin, R. P., Colomeacute, L. M., Guterres, S. S., & Pohlmann, A. R. (2007). Enteric Controlled-Release Pantoprazole-Loaded Microparticles Prepared by Using Eudragit S100 and Poly(ε-caprolactone) Blend. Pharmaceutical Development and Technology, 12(5), 463-471.
Raso, J., Pagan, R., Condon, S., & Sala, F. J. (1998). Influence of Temperature and Pressure on the Lethality of Ultrasound. Appl Environ Microbiol, 64(2), 465-471.
Ren, S., Park, M. J., Sah, H., & Lee, B. J. (2008). Effect of pharmaceutical excipients on aqueous stability of rabeprazole sodium. Int J Pharm, 350(1-2), 197-204.
Rhee, Y. S., Park, C. W., Shin, Y. S., Kam, S. H., Lee, K. H., & Park, E. S. (2008). Application of instrumental evaluation of color for the pre-formulation and formulation of rabeprazole. Int J Pharm, 350(1-2), 122-129.
Riedel, A., & Leopold, C. S. (2005). Degradation of omeprazole induced by enteric polymer solutions and aqueous dispersions: HPLC investigations. Drug Dev Ind Pharm, 31(2), 151-160.
Riegelman, S., & Collier, P. (1980). The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokinet Biopharm, 8(5), 509-534.
Roche, V. F. (2006). The chemically elegant proton pump inhibitors. Am J Pharm Educ, 70(5), 101.
Rowe, R. C., Sheskey, P. J., & Owen, S. C. (2006). Handbook of pharmaceutical Excipients (FIFTH ed.): Pharmaceutical Press and American Pharmacists Association.
Shi, S., & Klots, U. (2008). Proton pump inhibitors: an update of their clinical use and pharmacokinetics. European Journal of Clinical Pharmacology, 64(10), 935-951.
Shoaib, M. H., Tazeen, J., Merchant, H. A., & Yousuf, R. I. (2006). Evaluation of drug release kinetics from ibuprofen matrix tablets using HPMC. Pakistan Journal of Pharmaceutical Sciences, 19(2), 119-124.
Siepmann, J., & Gopferich, A. (2001). Mathematical modeling of bioerodible, polymeric drug delivery systems. Adv Drug Deliv Rev, 48(2-3), 229-247.
Stedman, C. A., & Barclay, M. L. (2000). Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther, 14(8), 963-978.
Su, Z., Sun, F., Shi, Y., Jiang, C., Meng, Q., Teng, L., et al. (2009). Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly(D,L-lactide-co-glycolide) microsphere. Chem Pharm Bull (Tokyo), 57(11), 1251-1256.
Suslick, K. S. (1988). Ultrasound:its chemical, physical and biological effects. VCH Publishers, Inc., New York, N.Y.
Suslick, K. S. (1990). Sonochemistry. Science, 247, 1439-1445.
Tetsuro, T., Tadashi, M., Toshio, K., Shinichiro, H., Nobuyuki, K., & Hajime, T. (1992). Stabilization of a new antiulcer drug (Lansoprazole) in the solid dosage forms. Drug Development and Industrial Pharmacy, 18(13), 1437-1447.
Thummala, A. S., Leach, J. K., & O''Rear, E. A. (2003). Factors affecting the particle size and in vitro release of bovine serum albumin from polyethylene glycol microparticles. Biomed Sci Instrum, 39, 318-323.
USP. (2006). US Pharmacopeial Convention, Rockville, MD, Monograph 1061: Color-Instrumental Measurement. US Pharmacopeia 29.
Vandegaer, J. E. (1974). Microencapsulation:Processes and Applications. New York: Plenum Press.
Vasir, J. K., Tambwekar, K., & Garg, S. (2003). Bioadhesive microspheres as a controlled drug delivery system. International Journal of Pharmaceutics, 255(1-2), 13-32.
Welage, L. S. (2003). Pharmacologic features of proton pump inhibitors and their potential relevance to clinical practice. Gastroenterology Clinics of North America, 32(3), 25-35.
Welage, L. S., & Berardi, R. R. (2000). Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc, 40(1), 52-62.
Wichert, B., & Rohdewald, P. (1990). A New Method for the Preparation of Drug Containing Polylactic Acid Microparticles without Using Organic-Solvents. Journal of Controlled Release, 14(3), 269-283.
Wischke, C., & Schwendeman, S. P. (2008). Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm, 364(2), 298-327.
Woodward, S. C., Brewer, P. S., Moatamed, F., Schindler, A., & Pitt, C. G. (1985). The intracellular degradation of poly(epsilon-caprolactone). J Biomed Mater Res, 19(4), 437-444.
Zhang, X. W., Sun, N. Y., Wu, B. J., Lu, Y., Guan, T. Z., & Wu, W. (2008). Physical characterization of lansoprazole/PVP solid dispersion prepared by fluid-bed coating technique. Powder Technology, 182(3), 480-485.
Zweers, M. L., Grijpma, D. W., Engbers, G. H., & Feijen, J. (2003). The preparation of monodisperse biodegradable polyester nanoparticles with a controlled size. J Biomed Mater Res B Appl Biomater, 66(2), 559-566.
行政院衛生署. (2005). 藥品安定性試驗基準. 藥政法規.

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