博碩士論文 943204062 詳細資訊




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姓名 林育生(Yu-sheng Lin)  查詢紙本館藏   畢業系所 化學工程與材料工程學系
論文名稱 蔗糖的同質異構型構
(Two Conformational Polymorphs of Sucrose)
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摘要(中) 在這篇論文中我們有六個觀點去證明我們的研究 (1) 證明蔗糖有第二種同質異構型構,(2) 使用23種在製藥界上常用純溶劑使用在糖類篩選上, (3)使用固態分析法(SSNMR, SXD) 去證明蔗糖的第二種型態, (4) DSC上顯示在150℃上波峰的固態-固態間傳遞,且蔗糖有兩種同質異構型構之間變換,從第二種型構轉成第一種型構, (5)利用再結晶法使用反溶劑(甲醇)製造第二種型構的蔗糖, (6) 研究蔗糖的同質異構型構當做配方在藥物載體上的影響, 在這篇論文中有三個重要的方向被用來增進整個糖業研發的效率。 首先我們利用使用23種有機溶劑篩選的方式,有關蔗糖溶解度(solubility)、多型晶體(polymorph)、晶體外貌(crystal habit)、以及結晶度(crystallinity)的資料被完整收集。 一種粗糙但簡單方便且只需要少量樣品的篩選方法也將在本論文中介紹。 第二,我們利用數種儀器法例如熱分析法(DSC)、固態核磁共振儀 (SSNMR)、單晶繞射儀 (SXD)、卡爾費雪水份滴定分析法(KF)和數位式折射計去證明蔗糖的同質異構型構。 第三,我們研究把蔗糖當作藥物載體去影響藥物的釋放速率。 我們可以預期型構一和型構二的蔗糖將會影響藥物的釋放速率對製藥界影響甚大。
摘要(英) In this thesis, we listed six points to demonstrate the significance of the work (1) the identification of conformational polymorph of FormⅡ sucrose, (2) using 23 kinds of pure solvents commonly used in pharmaceutical technology in sugar screening, (3) using solid-state instrumental methods (SSNMR, SXD) to demonstrate the presence of Form II sucrose, (4) showing that the DSC peak at 150°C was the enthalpy of the solid-solid transformation between the two conformational polymorphs of sucrose crystals changing from Form II to Form I, (5) using anti-solvent (methanol) for re-crystallizing Form II sucrose, (6) investigated the influence conformational polymorphs of sucrose as an excipient in the formulation. Three important studies in this thesis were performed to improve the efficiency of the discovery and development process. Firstly, a useful engineering data bank of solubility, polymorphism, crystal habits and crystallinity by initial solvent screening for sucrose was be established and a robust, miniature solvent screening method was be introduced. Secondly, we used several instrumental methods to demonstrate the presence of conformational polymorph of FormII sucrose such as differential scanning calorimetry (DSC), solid-state NMR (SSNMR), single-crystal x-ray, diffractometer (SXD), Karl Fischer titrimetry (KF) ,and refractometer sensor. Thirdly, we investigated the influence of sucrose in formulation as an excipient. We expect that FormⅠand FormⅡ sucrose crystals will affect the drug release rate.
關鍵字(中) ★ 蔗糖的同質異構型構
★ 蔗糖
關鍵字(英) ★ Conformational Polymorphs of Sucrose
★ Sucrose
論文目次 摘要………………………………………………………………………………………I
Abstract………………………………………………………………………………… II
Acknowledgments…………………………………………………………………….. IV
Table of Contents………………………………………………………………………..V
List of Figures………………………………………………………………………….IX
List of Tables…………………………………………………………………………XVI
Chapter 1 Executive summary…………………………………………………………..1
1.1 Introduction…………………………………………………………….….…1
1.2 Brief Introduction of Sucrose………………………………………….……..6
1.3 Conceptual Framework………………………………………………….…...7
References………………………………………………………………………...11
Chapter 2 Analytical Instruments…………………..……………………………….…16
2.1 Introduction………………………………………………………………….16
2.2 Thermal Analysis…………………………………………………………....19
2.2.1 Differential Scanning Calorimetry (DSC)……………………………19
2.2.2 Thermogravimetry Analysis (TGA)………………………………….22
2.3 Spectroscopic Identification………………………………………………....24
2.3.1 Fourier Transform Infrared (FT-IR) Spectroscopy…………………...24
2.3.2 Solid-State NMR Measurements (SSNMR)………………………...26
2.3.3 Ultraviolet and Visible Spectroscopy (UV/Vis)……………………..29
2.4 Crystallography……………………………………………………………….32
2.4.1 X-ray powder diffractometry (PXRD)………………………............32
2.4.2 Single-Crystal X-Ray Diffractometer (SXD)………………………..35
2.5 Microscopic Methods…………………………………...…………………..35
2.6 The refractometer sensor…………………………………………...……….41
2.7 Karl Fischer Titration……………………………………………………….43
2.8 References……………..………………...………………………………….47
Chapter 3 Initial Solvent Screening of Sucrose: Solubility, Polymorphism, Crystal habits, and Crystallinity……………………………………………………..55
3.1 Introduction………………………...………………………………………..55
3.1.1 Solubility…………………………………………………………….56
3.1.2 Polymorph…………………………………………………………...58
3.1.3 Crystal habit…………………………………………………………61
3.1.4 Crystallinity………………………………………………………….61
3.2 Materials……………….…………………………………………………….62
3.3 Experiment…………………………………………………………………..68
3.3.1 Solubility Test……………………………………………..………....68
3.3.2 Anti-solvent Test…………………………………………………….69
3.3.3 Polymorph and Morphology Instrumental Study………..…………..70
3.4 Results and Discussion.……………………………………………………...73
3.4.1 Polymorph study………………………….………………………....73
3.4.2 Morphology Study………………………………...…………………81
3.4.3 Solubility Analysis…………………………………………………..85
3.4.4 Temperature Diagram for Sucrose Polymorphs Study………………89
3.5 Conclusions……………………………………………………………….....91
References………………………………………………………………………...93
Chapter 4 Identification Form II Conformational Polymorphs of Sucrose…….…….101
4.1 Introduction………………………………………………………………...101
4.2 Materials ……………..…………………………………………………….105
4.3 Experiment Methods…………………………………….…………………106
4.3.1 Preparation of Form II Sucrose Samples………………..………....106
4.3.2 OM Analysis………………….……………………………………106
4.3.3 Standard Sucrose Solutions and Calibration Curve Study…………107
4.3.4 Saturation Sucrose Solutions……………………………………….107
4.3.5 Polymorph Instrumental Study……………………………………..108
4.4 Results and Discussion.…………………………………………………….111
4.4.1 Solid-State NMR (SSNMR) Study….……………………………...111
4.4.2 Single-Crystal X-ray Diffractometer (SXD)……………………….114
4.4.3 Low Scanning Speed DSC Study………………..…………………118
4.4.4 High Scanning Speed DSC Study………………………………….119
4.4.5 Solubility Curve Study……………………………………………..120
4.5 Conclusions………………………………………………………………...123
References……………………………………………………………………….124
Chapter 5 Dissolution Study………………………………………………………...131
5.1 Introduction………………………………………………………………..131
5.2 Materials…………………………………………………………………...134
5.3 Experimental Methods…………………………………………………….134
5.3.1 Preparation of Samples…………….……………………………….134
5.3.2 Dissolution Tests…………………………………………………...136
5.4 Results and Discussion..…………………………………………………...139
5.4.1 Sample Analysis……………………………………………………...139
5.4.2 Dissolution Test………………………………………………………147
5.5 Conclusions……………..………………………………………………....146
Chapter 6 Conclusions and Future Works……………………………………….153
Summary of references………………………………………………………...……...156
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指導教授 李度(Tu-Lee) 審核日期 2007-7-20
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