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研究生: 林育生
Yu-sheng Lin
論文名稱: 蔗糖的同質異構型構
Two Conformational Polymorphs of Sucrose
指導教授: 李度
Tu-Lee
口試委員:
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程與材料工程學系
Department of Chemical & Materials Engineering
畢業學年度: 95
語文別: 英文
論文頁數: 157
中文關鍵詞: 蔗糖的同質異構型構蔗糖
外文關鍵詞: Conformational Polymorphs of Sucrose, Sucrose
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  • 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。


    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.

    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

    Chapter 1
    1. P. Honig, “Chemical properties of sucrose,” Chapter 1 of principle of sugar
    technology 1st ed, (West Indies Sugar Corporation, New York, USA, 1965),
    pp1-8
    2. http:// 64.233.179.104/translate 中天期貨 Joint Future
    3. 陳治玄,“登糖入室,”台灣糖業研究所“科學發展”384, 56-61 (2004)
    4. P. Honig, chapter 1 “Chemical properties of sucrose,” Principle of sugar
    technology ,1st ed, Technical Research Director West Indies Sugar Corporation,
    New York, USA, 1965, pp24-25
    5. S. V. Shah, and Y. M. Chakradeo “A note of the melting point of cane sugar,”
    Current Sci.,4, p652 (1936)
    6. P. Fryer and K. Pinschower, “The materials science of chocolate,” MRS Bull.,
    25(12), 25-29 (2000)
    7. A. Saleki-Gerhardt and G. Zografi, “Non-isothermail crystallization of sucrose
    from the amorphous state,” Pharm. Res., 11(8), 1166-1173 (1994)
    8. J. C. P. Chen, “The crystallization of sugar,” Chapter 10 of cane sugar handbook
    11th ed, (International Sugar Consultant, New York, USA, 1965), pp276-343
    9. M. Okuno, S. Kishihara, M. Otsuka, S. Fujill, and K. Kawasaki, “Variability of
    melting behavior of commercial granulated sugar measured by differential
    scanning calorimetry,” Int. Sugar J., 105(1249), 29-35 (2003)
    10. M. Hurtta, I. Pitkanen, and J. Knuutinen, “ Melting behaviour of D-sucrose,
    D-glucose and D-fructose,” Carbo. Res., 339(13), 2267–2273 (2004)
    11. S. T. Beckett, M. G. Francesconi, P. M. Geary, G. Mackenziea and A. P. E.
    Maulny, “DSC study of sucrose melting,” Carbo. Res., 341(15), 2591–2599
    (2006)
    12. P. Honig, “Chapter 1 in chemical properties of sucrose,” Principle of sugar
    technology ,1st ed, (West Indies Sugar Corporation, New York, USA, 1965),
    pp24-25
    13. G.. Eggleston, B. J. Trask-Morrell, and J. R. Vercellotti, “Use of differential
    scanning calorimetry and thermogravimetric analysis to characterize the thermal
    degradation of crystalline sucrose and dried sucrose-salt residues,” J. Agric. Food Chem., 44(10), 3319-3325 (1996)
    14. B.I.M. Grimsey, and T. M. Herrington, “The formation of inclusions in sucrose
    crystals,” Int. Sugar J., 96(1152), 504-514 (1994)
    15. N. Blagden, R. J. Davey, H. F. Lieberman, L. William, R. Payne, R. Roberts, R.
    Rowe and R. Docherty, “Crystal chemistry and solvent effects in polymorphic
    systems sulfathiazole,” J. Chem. Soc., Faraday Trans., 94(8), 1035-1044 (1998)
    16. M. Lahav and L. Leiserowitz, “The effect of solvent on crystal growth and
    morphology,” Chem. Eng. Sci., 56(7), 2245-2253 (2001)
    17. T. Threfall, “Crystallization of polymorphs: thermodynamic insight into the role
    of solvent,” Org. Process Res. Dev., 4(5), 384-390 (2000)
    18. D. Giron, “Thermal analysis and calorimetric methods in the characterization of
    polymorphs and solvates,” Thermochem. Acta, 248(2), 1-59 (1995)
    19. A. J. Wright, S. E. McGauley, S. S. Narine, W. M. Willis, R. W. Lencki, and A. G.
    Marangoni, “Solvent effects on the crystallization behavior of milk fat fractions”
    J. Agric. Food Chem., 48(4), 1033-1040 (2000)
    20. S. L. Morissettea, O. Almarssona, M. L.Petersona, J. F. Remenara, M. J. Reada,
    A. V. Lemmoa, S. Ellisa, M. J. Cimab, and C. R. Gardnera, “High-throughput
    crystallization: polymorphs, salt, co-crystals and solvates of pharmaceutical
    solids,” Adv. drug Del. Rev., 56(3), 275-300 (2004)
    21. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar
    technology 1rd ed, (West Indies Sugar Corporation: New York, USA, 1965),
    pp2-3
    22. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar
    technology 1st ed, (West Indies Sugar Corporation: New York, USA, 1965),
    pp1-3
    23. M. S. Jeffery “Key functional properties of sucrose in chocolate and sugar
    confectionery,” Food Tech., 47(1-3), 141-144 (1993)
    24. A. Awad and A. C. Chen, “A new generation of sucrose products made by
    cocrystallization,” Food Tech., 47(1-3), 146-148 (1993)
    25. A. A. Joshi and X. Duriez, “ Added functionality excipients: an answer to
    challenging formulations,” Pharm. Tech., 12, 12-19 (2004)
    26. R. Hilfiker, “Relevance of solid-state properties for pharmaceutical products ,”
    Chapter 1 of Polymorphism, (In the pharmaceutical industry, 1st Ed, Weinheim,
    2006), pp13-14
    27. M. L. P. Leitao, J.Canotilho, M. S. C.Cruz, J. C. Pereira, A.T. Sousa, and J. S. Redinha, “Study of polymorphism from DSC melting curves,” J. Therm. Anal.
    Calorim., 68(2), 397-412 (2002)
    28. C. McGregor, M. H. Saunders, G. Buckton , and R. D. Saklatvala, “The use of
    high-speed differential scanning calorimetry (Hyper-DSCTM) to study the
    thermal properties of carbamazepine polymorphs,” Thermochim. Acta, 417(2),
    231–237 (2004)
    29. R. Hilfiker, “Characterization of polymorphic systems using thermal analysis,”
    Chapter 3 of Polymorphism, In the pharmaceutical industry, 1st ed., Weinheim,
    2006, pp71
    30. S. R. Byrn, P. A. Sutton, B. Tobias, J. Frye, and P. Main, “The crystal structure,
    solid-state NMR Spectra, and oxygen reactivity of five crystal forms of
    prednisolone tert-butylacetatet,” J. Am. Chem. Soc., 110(5), 1609-1614 (1988)
    31. U. R. Desai, I. R. Vlahov, A. Pervin, and R. J. Linhardt, “Conformational
    analysis of sucrose octasulfate by high resolution nuclear magnetic resonance
    spectroscopy,” Carbo. Res., 275(2), 391-401 (1995)
    32. B. E. Padden, M. T. Zell, Z. Dong, S. A. Schroeder,D. J. W. Grant, and E.J.
    Munson, “Comparison of solid-state 13C NMR spectroscopy and powder X-ray
    diffraction for analyzing mixtures of polymorphs of neotame,” Anal. Chem.,
    71(16), 3325-3331 (1999)
    33. D. K. Kondepudi, and K. E. Crook, “Theory of conglomerate crystallization in
    the presence of chiral impurities,” Cryst. Growth Des., 5(6), 2173-2179 (2005)
    34. B. Rodrıguez-Spong, C. P. Price, A. Jayasankar, A. J. Matzger, and N.
    Rodrıguez-Hornedo, “General principles of pharmaceutical solid polymorphism:
    a supramolecular perspective,” Advanced Drug Del Rev., 56(2), 241– 274 (2004)
    35. P.T Cardew, and R. J. Davey, “The kinetics of solvent-mediated phase
    transformation,” Math. Phys. Sci., 398(1815), 415-428 (1985)
    36. C. R. Chen, Y. H. lin, S. L. Cho, S. H. Yen, and H. L. S. Wu, “ Investigation of
    the dissolution difference acidic and neutral media of acetaminophen tables
    containing a super distintegrant and a soluble excipient,” Chem. Pharm. Bull.,
    45(3), 509-512 (1997)
    Chapter 2
    1. H.Gloria, and D. Sievert, “Changes in the physical state of sucrose during dark
    chocolate processing,” J.Agric. Food Chem., 49(5), 2443-2436 (2001)
    2. T. Yoshinari, R.T. Forbes, P. York, and Y. Kawashima, “Moisture induced
    polymorphic transition of mannitol and its morphological transformation,” Int. J.
    of Pharm., 247(1-2), 69-77 (2002)
    3. L. Yu, N. Milton, E. G. Groleau, D. S. Mishra, and R. E. Vansickle, “Existence
    of a mannitol hydrate during freeze-drying and practical implications,” J. Pharm.
    Sci., 88(2), 196-198 (1999)
    4. T.Yoshinari, R.T. Forbes, P. York, and Y. Kawashima, “Moisture induced
    polymorphic transition of mannitol and its morphological transformation,” Int. J.
    Pharm., 247(9), 69-77 (2002)
    5. P. Di Martino, A-M. Guyot-Hermann, P. Conflant, M. Drache, and J-C. Guyot,
    “A new pure paracetamol for direct compression:the orthorhombic form,” Int. J.
    Pharm., 128(1-2), 1-8 (1996)
    6. M. Okuno, S. Kishihara, M. Otsuka, S. Fujill, and K. Kawasaki, “Variability of
    melting behavior of commercial granulated sugar measured by differential
    scanning calorimetry,” Int. Sugar. J., 105(1249) 29-35 (2003)
    7. M. Hurtta, I. Pitkanen, and J. Knuutinen, “Melting behavior of D-sucrose,
    D-glucose and D-fructose,” Carbo. Res., 339(13), 2267–2273 (2004)
    8. S. T. Beckett, M. G. Francesconi, P. M. Geary, G. Mackenziea, and A. P. E.
    Maulny, “DSC study of sucrose melting,” Carbo Res., 341(15), 2591–2599
    (2006)
    9. P. Fryer, and K. Pinschower, “The materials Science of Chocolate,” MRS Bull.,
    25(12), 25-29 (2000)
    10. L. Yu, S. M. Reutzel, and G. A. Stephenson, “Physical characterization of
    polymorphic drugs: an integrated characterization strategy,” PSTT 1(3), 118-127
    (1998)
    11. K. L. A. Chan, and S. G. Kazarian, “Fourier transform infrared imaging for
    high-throughput analysis of pharmaceutical formulation,” J. Comb. Chem., 7(2),
    185-189 (2005)
    12. T. C. Huang, “Automatic X-ray single crystal structure analysis system for small
    molecule,” The Rigaku J., 21(2), 43-46 (2004)
    13. M. J. Arias, J. M. Gines, J. R. Moyano, J. I. Perez-Martinez, and A. M. Rabasco,
    “Influence of the preparation method of solid dispersions on their dissolution
    rate:study of triamterene D-mannitol system,” Int. J. of Pharm., 123(1), 25-31
    (1995)
    14. B.Snider, P. Liang, and N. Pearson, “Implementation of water-activity testing to
    replace Karl Fischer water testing for solid oral-dosage forms,” Pharm. Tech.,
    31(2), 1-10 (2007)
    15. L. A. Peter, and P. L. G.. Christopher, “The effect of hexose upon pol, brix and
    calculated CCS in sugarcane: a potential for negative pol bias in juice from
    actively growing cane,” J. Am. Soc. S. Cane Tech., 24(4), 185-198 (2004)
    16. L. Yu, S. M. Reutzel, and G. A. Stephenson, “Physical characterization of
    polymorphic drugs: an integrated characterization strategy,” Pharm. Sci. Tech.
    Today, 1(3), 118-127 (1998)
    17. P. J. Haines, and F. W. Wilburn, “Thermal methods of analysis- principles
    differential,” Chapter 3 of Thermal Analysis and Differential Scanning
    Calorimetry, Applications and Problems, 1st ed, Blackie Academic and
    Professional, New York, USA, 1995, pp.63- 89
    18. E. V. Boldyerva, V. A. Drebushchak, I. E. Paukov, Y. A. Kovalevskaya, and T. N.
    Drebushchak, “DSC and adiabatic calorimetry study of the polymorphs of
    paracetamol,” J. of Therm. Anal. Calor., 77(2), 607-623 (2004)
    19. T. L. Threlfall, “Analysis of organic polymorphs : A Review,” The analyst,
    120(10), 2435-2460 (1995)
    20. D. Giron, “Thermal analysis and calorimetric methods in the characterization of
    polymorphs and solvate,” Thermochim. Acta, 248(2), 1-59 (1995)
    21. A. J. Pasztor, “Thermal analysis techniques,” Chapter 50 of Handbook of
    Instrumental Techniques for Analytical chemistry, F. A. Settle, Prentice Hall PTR,
    New Jersey, USA, 1997, pp.909-917
    22. P. J. Haines, and F. W. Wilburn, “Differential thermal analysis and differential
    scanning calorimetry,” Chapter 3 of Thermal Methods of Analysis- Principles, 5th
    ed, Applications and Problems, Peter J. Haines, Blackie Academic and
    Professional, New York, USA, 1995, pp.63- 89
    23. B. R. Spong, C. P. Price, A. Jayasankar, A. J. Matzger, and N. R. Horndo,
    “General principles of pharmaceutical solid polymorphism a supramolecular
    perspective,” Adv. Drug Del. Rev., 56(3), 241-274 (2004)
    24. K. Urakami, Y. Shono, A. Higashi, K. Umemoto, and M. Godo, “A novel method
    for estimation of transition temperature for polymorphic pairs in pharmaceuticals
    using heat of solution and solubility data,” Chem. Pharm. Bull., 50(2), 263-267
    (2002)
    25. T. Hatakeyama, and Z. Liu, “Conformation of TA apparatus,” Chapter 2 of
    Handbook of Thermal Analysis, 1st ed, John Wiley & Sons, Baffins Lane,
    England, 1998, pp.17-19
    26. G.. Eggleston, B. J. Trask-Morrell, and J. R. Vercellotti, “Use of differential
    scanning calorimetry and thermogravimetric analysis to characterize the thermal
    degradation of crystalline sucrose and dried sucrose-salt residues,” J. Agric.
    Food Chem., 44(10), 3319-3325 (1996)
    27. D. A. Skoog, F. J. Holler, and T. A. Nieman, Principles of instrucmental analysis,
    5th ed, Thomson Learnin, Mississippi, USA, 2001, pp.182-183
    28. F. Rouessac, and A. Rouessac, “Chemical analysis- modern instrumentation
    methods and Techniques,” Chapter 10 of Infrared Apectroscopy, 1st ed, John
    Willy & Sons, chichester, England, 2001, pp.170-173
    29. H. Takahashi, R. Chen, H. Okamoto, and K. Danjo, “Acetaminophen particle
    design using chitosan and a spray-drying technique,” Chem. Pharm. Bull., 53(1),
    37-41 (2005)
    30. D. L. Pavia, G. M. Lampman, and G. S. Kriz, “Introduction to spectroscopy: a
    guide for students of origanic chemistry,” Chapter 2 of Infrared Spectroscopy, 1st
    ed, Thomson Learning, Inc., USA, 2001, pp.45-68
    31. J. W. Lubach, and E. J Munson, “Solid-state spectroscopy,” Chapter 4 of
    Polymorphism, In the pharmaceutical industry, 1st ed, Weinheim, R. Hilfiker,
    Germany, 2006, pp.81-82
    32. J. W. Lubach, and E. J Munson, “Solid-state spectroscopy,” Chapter 4 of
    Polymorphism, In the pharmaceutical industry, 1st ed, Weinheim, R. Hilfiker,
    Germany, 2006, pp.83-84
    33. T. J. Offerdahl, “Solid-State Nuclear Magnetic Resonance Spectroscopy for
    Analyzing Polymorphic Drug Forms and Formulations,” Pharm. Tech., 30(2),
    24-42 (2006)
    34. L. R. Chen, B. E. Padden, S. R. Vippagunta, E. J. Munson, and D. J. W. Grant,
    “Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil
    hydrates,” Pharm. Res., 17(5), 619-624 (2000)
    35. T. L. Threlfall, “Analysis of organic polymorphs a review,” Anal. Oct., 120(17),
    2435-2460 (1995)
    36. J. W. Lubach, and E. J Munson, “Solid-state spectroscopy,” Chapter 4 of
    Polymorphism, 1st ed, In the pharmaceutical industry: Weinheim, Germany, 2006,
    pp82-84
    37. M. Sezlagiewicz, C. Marcolli, S. Cianferani, A. P. Hard, A. Vit, A. Burkhard,
    M.von Raumer, U. Ch. Hofmeier, A. Zilian, E. Francotte, and R. Schenker, “ In
    situ characterization of polymorphic forms,” J. of Therm. Anal. and Calor., 57(1),
    23-43 (1999)
    38. T. W. Adorno, “The form of the phonograph record,” JSTOR Arts and Sciences October, 55, 56-61 (1990)
    39. J. McMurry, “In chapter 14 Conjugested dienes and ultraviolet spectroscopy,”
    Organic Chemistry, 6th ed, Thomson Learning, USA, pp.482-484, 2004
    40. D. A. Skoog, F. J. Holler, and T. A. Nieman, “An introduction to ultraviolet/
    visible molecular absorption spectrometry,” Chapter 13 of Principles of
    Instrucmental Analysis, 5th ed, Thomson Learnin., USA, 2001, pp300-306
    41. J. A. Howell, “Ultraviolet and visible molecular absorption spectrometry,”
    Chapter 25 of Handbook of Instrumental Techniques for Analytical chemistry, F.
    A. Settle, Prentice Hall PTR, New Jersey, USA, 1997, pp.481-493
    42. D. L. Pavia, G. M. Lampman, and G. S. Kriz, “In chapter 7 Ultraviolet
    Spectroscopy,” Introduction to spectroscopy: a guide for students of origanic
    chemistry, 3rd ed, Thomson Learnin., USA, 2001, pp3535-3545
    43. M. J. Ayora Cañada, M. I. P. Reguera, A. Mo. Diaz, and L. F. C.Vallvey,
    “Solid-phase UV spectroscopic multisensor for the simultaneous determination
    of caffeine, dimenhydrinate and acetaminophen by using partial least squares
    multicalibration,” Talanta, 49(3), 691-701 (1999)
    44. J. Formica, “X-ray diffraction,” Chapter 18 of Handbook of Instrumental
    Techniques for Analytical chemistry, edited by F. A. Settle, Prentice Hall PTR,
    New Jersey, USA, pp.339-353 (1997)
    45. T. C. Huang, “Automatic x-ray single crystal structure analysis system for small
    molecule,” The Rigaku J., 21(2), 43-46 (2004)
    46. T. C. Kriss, V. M. Kriss, and M.Vesna, “History of the operating microscope:
    from magnifying glass to microneurosurgery,” Neu., 42(4), 899-907 (1998)
    47. K. Gotoh, H. Masuda, and K. Higashitani, “Powder-handling operation,” Chapter
    5 of Powder Technology Hand Book, 2nd ed, USA, 1997, pp720-730
    48. K. Gotoh, H. Masuda, and K. Higashitani, “Fundamental properties of powder
    Beds,” Chapter 3 of Powder Technology Hand Book, 2nd ed, USA, 1997,
    pp.413-423
    49. K. Gotoh, H. Masuda, and K. Higashitani, “Powder-handling operation,” Chapter
    5 of Powder Technology Hand Book, 2nd ed, USA, 1997, pp.659-661
    50. http://micro. Magnet. Fsu.edu/ optics/lightandcolor/lenses.htm, “Introduction to
    lenses.”
    51. S. Mccarthy, and J.Billingsley, “A sensor for the sugar cane harvester topper,”
    Sen. Rev., 22(3), 242-246 (2002)
    52. H.S. Lu, H. R.Xu, Y.B. Ying, X. P. Fu, H. Y. Yu, and H. Q. Tian, “Application fourier transform near infrared spectrometer in rapid estimation of soluble solid
    content of intact citrus fruits,” J. Z. Univ. Sci. B 7(10), 794-799 (2006)
    53. J. E. Brown, and B. G.. Liptack, “Refractometer,” in Liptak, B. G.. (ED.), Process
    measurement and analysis, Randnor, PA, 1995, pp 1191-1196
    54. K. Schroeder, W. Ecke, R. Mueller, R. Willsch, and A. Andreev, “A fibre bragg
    grating refractometer,” Meas. Sci. Technol., 12(7), 757-764 (2001)
    55. S. A. Margolis, “Amperometric measurement of moisture in transformer oil
    using Karl Fischer reagents,” Anal. Chem., 67(23), 4239-4246 (1995)
    Chapter 3
    1. Y. Akpalu, L. Kielhorn, B. S. Hsiao, R. S. Stein, T. P. Russell, J. V. Egmond, and
    M. Muthukumar, “Structure development during crystallization of homogeneous
    copolymers of ethene and 1-octene: time-resolved synchrotron x-ray and SALS
    measurements,” Macromol., 32(3), 765-770 (1999)
    2. H. Ahari, Robert L. Bedard, Carol L. Bowes,Neil Coombs, G.. A. Ozin, S.Petrov,
    I. Sokolov, A. Verma, Gregory Vovk, and D. Young, “Effect of microgravity on
    the crystallization of a selfassembling layered material,” Nat., 388(6645),
    857-860 (1997)
    3. A. J. Wright, S. E. Mcgauley, S. S. Narine, W. M. Willis, R.W. Lencki, and A. G..
    Marangoni, “Solvent effect on the crystallization behavior of milk fat fractions,”
    J. Agric. Food Chem., 48(4), 1033-1040 (2000)
    4. K. Gotoh, H. Masuda, and K. Higashitani, “Preparation of powder,” Chapter 6 of
    Powder Technology Hand Book, 2nd ed, Marcel Deekker, New York, USA, 1997,
    pp459-468
    5. S. L. Morissettea, O. Almarssona, M. L.Petersona, J. F. Remenara, M. J. Reada,
    A. V. Lemmoa, S. Ellisa, M. J. Cimab, and C. R. Gardnera, “High-throughput
    crystallization: polymorphs, salt, co-crystals and solvates of pharmaceutical
    solids,” Adv. drug Del. Rev., 56(3), 275-300 (2004)
    6. A. J. Wright, S. E. McGauley, S. S. Narine, W. M. Willis, R. W. Lencki, and A. G.
    Marangoni, “Solvent effects on the crystallization behavior of milk fat fractions,”
    J. Agric. Food Chem., 48(4), 1033-1040 (2000)
    7. A. Gracin, and A.C. Rasmuson, “Solubility of Phenylacetic acid,
    p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid,
    and ibuprofen in pure solvents,” J. Chem. Eng. Data, 47(6), 1379–1383 (2002)
    8. D. K. Kondepudi, and K. E. Crook, “Theory of conglomerate crystallization in
    the presence of chiral impurities,” Cryst. Growth Des., 5(6), 2173-2179 (2005)
    9. W.L. McCabe, J.C. Smith, and P. Harriott, “Mechanical separations,” Chapter 29
    of Unit Operations of Chemical Engineering, 6th ed, McGraw Hill Co, New York,
    USA, , 2001, pp.1017
    10. T. Threlfall, “Crystallisation of polymorphs: thermodynamic insight into the role
    of solvent,” Org. Process Res. Dev., 4(5), 384-390 (2000)
    11. B.C. Hancock et al., “Comparison of the mechanical properties of the crystalline
    and amorphous forms of a drug substance,” Int. J. Pharm., 241(1), 73–85 (2002)
    12. H. Egawa et al., “Solubility parameter and dissolution behavior of cefalexin
    powders with different crystallinity,” Chem. Pharm. Bull., 40(3), 819–820 (1992)
    13. P. D. Martino et al., “Influence of crystal habit on the compression and the
    densification mechanism of ibuprofen,” J. Crys. Growth., 243(2), 345–355
    (2002)
    14. W. Beckmann, “Seeding the desired polymorph: background, possibilities,
    limitations, and case studies,” Org. Process Res. Dev., 4(5), 372-383 (2000)
    15. M. Lahav, and L. Leiserowitz, “A stereochemical approach that demonstrates the
    effect of solvent on the growth of polar crystals: a perspective,” Crys. Growth
    Des. 6(3), 619–624 (2003)
    16. C-H Gu, V. Young, and D. J. W. Grant, “Polymorph screening : influence of
    solvents on the rate of solvent-mediated polymorphic transformation,” J. Pharm.
    Sci., 90(11), 1878-1890 (2001)
    17. L. Yu, S. M. Reutzel, and G. A. Stephenson, “Physical characterization of
    polymorphic drugs: an integrated characterization strategy,” PSTT, 1(3), 118-127
    (1998)
    18. B. Rodrıguez-Spong, C. P. Price, A. Jayasankar, A. J. Matzger, and N.
    Rodrıguez-Hornedo, “General principles of pharmaceutical solid polymorphism:
    a supramolecular perspective,” Advanced Drug Del Rev., 56(2), 241– 274 (2004)
    19. J. Bernstein, R. J. Davey, and J-O Henck, “Concomitant polymorphs,” Angew.
    Chem. Int. Ed., 38(23), 3440 – 3461 (1999)
    20. D. Giron, “Thermal analysis and calorimetric methods in the characterisation of
    polymorphs and solvates,” Thermochem. Acta., 248(2), l-59 (1995)
    21. C. Mao, R. Pinal, and K. R. Morris, “A quantitative model to evaluate solubility
    relationship of polymorphs from their thermal properties,” Pharm. Res., 22(7),
    1149-1157 (2005)
    22. L. Threlfall, “Analysis of organic polymorphs a review,” Anal., 120(10),
    2435-2460 (1995)
    23. P.T Cardew, and R. J. Davey, “The kinetics of solvent-mediated phase
    transformation,” Math. Phys. Sci., 398(1815), 415-428 (1985)
    24. K. Sato, “Polymorphic transformations in crystal growth,” J. Phys. D Awl. Phys.,
    26(8) B77-84 (1993)
    25. K. Pack, J. M. B. Evans, and A. S. Myerson, “Determination of solubility of
    polymorphs using differential scanning calorimetry,” Cryst. Growth Des., 3(6),
    991-995 (2003)
    26. A. K. Tiwary, “Modification of crystal habit and its role in dosage form
    Performance,” Drug Dev. Ind. Pharm., 27(7), 699-709 (2001)
    27. N. Blagden, R. J. Davey, H. F. Lieberman,L. William, R. Payne, R. Roberts, R.
    Rowe, and R. Docherty, “Crystal chemistry and solvent effects in polymorphic
    systems sulfathiazole,” J. Chem. Soc., Faraday Trans., 94(8), 1035-1044 (1998)
    28. M. Lahav, and L. Leiserowitz, “The effect of solvent on crystal growth and
    morphology,” Chem. Eng. Sci., 56(7), 2245-2253 (2001)
    29. N. Rasenack, and B. W. Muller, “Crystal habit and tableting behavior,” Int. J.
    Pharm., 244(1-2), 45-57 (2002)
    30. D. Gao, and J. H. Rytting, “Use of solution calorimetry to determine the extent of
    crystallinity of drugs and excipients,” Int. J. Pharm., 151(2), 183-192 (1997)
    31. Y. Kong, and J. N. Hay, “The enthalpy of fusion and degree of crystallinity of
    polymers as measured by DSC,” Eur. Polym. J., 39(8), 1721-1727 (2003)
    32. F. Giordano1, A. Rossi1, R. Bettini1, A. Savioli1, A. Gazzaniga, and Cs. Novák,
    “Thermal behavior of paracetamol-polymeric excipients mixtures,” J. Therm.
    Anal. Calor., 68(2), 575-590 (2002)
    33. M. Garcia, G. Vliet, M. G. J. ten Cate, F. Chavez, B. Norder, B. Kooi, W. E. van
    Zyl, H. Verweij, and H. A. Blank “Large-scale extrusion processing and
    characterization of hybrid nylon-6/SiO2 nanocomposites,” Polym. Adv. Technol.,
    15(4), 164-172 (2004)
    34. A. A. Lacey, D. M. PRICE, and M. Reading, “Theory and practice of modulated
    temperature differential scanning calorimetry,” Annu. Rev. Phys. Chem., 47(1),
    243-282 (1996)
    35. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar technology, 1st ed., (Technical Research Director West Indies Sugar Corporation,
    New York, USA, 1965), pp24-25
    36. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar
    technology, 1st ed., (Technical Research Director West Indies Sugar Corporation:
    New York, USA, 1965), pp1-8
    37. P. Fryer, and K. Pinschower, “The materials science of chocolate,” MRS Bull.,
    25(12), 25-29 (2000)
    38. A. Saleki-Gerhardt, and G. Zografi, “Non-isothermail crystallization of sucrose
    from the amorphous state,” Pharm. Res., 11(8), 1166-1173 (1994)
    39. M. S. Jeffery, “Key functional properties of sucrose in chocolate and sugar
    confectionery,” Food Tech., 47(1-3), 141-144 (1993)
    40. A. Awad, and A. C. Chen, “A new generation of sucrose products made by
    cocrystallization,” Food Tech., 47(1-3), 146-148 (1993)
    41. S. V. Shah, and Y. M. Chakradeo, “A note of the melting point of cane sugar,”
    Current Sci.,4, p652 (1936)
    42. J. C. P. Chen, “The crystallization of sugar,” Chapter 10 of Cane sugar handbook
    11th ed, (International Sugar Consultant, New York, USA, 1965), pp276-343
    43. M. Okuno, S. Kishihara, M. Otsuka, S. Fujill, and K. Kawasaki, “Variability of
    melting behavior of commercial granulated sugar measured by differential
    scanning calorimetry,” Int. Sugar. J., 105(1249), 29-35 (2003)
    44. M. Hurtta, I. Pitkanen, and J. Knuutinen, “Melting behaviour of D-sucrose,
    D-glucose and D-fructose,” Carbo. Res., 339(13), 2267–2273 (2004)
    45. S. T. Beckett, M. G. Francesconi, P. M. Geary, G. Mackenziea, and A. P. E.
    Maulny, “DSC study of sucrose melting,” Carbo. Res., 341(15),
    2591–2599(2006)
    46. D. J. C. Constable, C. Jimenez-Gonzalez, and R. K. Henderson, “Perspective on
    solvent use in the pharmaceutical industry,” Org. Process Res. Dev., 11(1),
    133-137 (2007)
    47. P. Barrett, B. Smith, J. Worlitschek, V. Bracken, B. O, Sullivan, and D. O, Grady,
    “A Review of the use of process analytical technology for the understanding and
    optimization of production batch crystallization processes,” Org. Process Res.
    Dev., 9(3), 348-355 (2005)
    48. P. Honig, “Physical properties of sucrose ,” Chapter 2 of Principle of sugar technology 1st ed, (Technical Research Director West Indies Sugar Corporation,
    USA, New York, 1965), pp21-22
    49. K. Kawakami, K. Miyoshi, N. Tamura, T. Yamaguchi, and Y. Ida,
    “Crystallization of sucrose glass under ambient conditions: evaluation of
    crystallization rate and unusual melting behavior of resultant crystals,” J. Pharm.,
    95(6), 1354-1363 (2006)
    50. H. Gloria, and D. Sievert, “Changes in the physical state of sucrose during dark
    chocolate processing,” J.Agric. Food Chem., 49(5), 2443-2436 (2001)
    51. G.. Eggleston, B. J. Trask-Morrell, and J. R. Vercellotti, “Use of differential
    scanning calorimetry and thermogravimetric analysis to characterize the thermal
    degradation of crystalline sucrose and dried sucrose-salt residues,” J. Agric.
    Food Chem., 44(10), 3319-3325 (1996)
    52. R. Jantas, and B. Delczyk, “Preparation characterisation and antibacterical
    properties of sucrose-1-naphtylacetic acid adduct,” Fibres ﹠Textiles in Eastem
    Europe., 13(1), 60-63 (2005)
    53. N. B. Colthup, L. H. Daly, and S. E. Wiberley, “Introduction to infrared and
    ramam spectroscopy,” 3rd ed, New York, USA, 1991,pp335-336
    54. M. Darder, and E. Ruiz-Hitzky, “Caramel-clay nanocomposites,” J. Mater.
    Chem., 15(9), 3913-3918 (2005)
    55. J. M. E. Bunyan, N. Shankland, and D. B. Sheen, “Solvent effect on the
    morphology of ibuprofen,” Particle Design via Crystallization AIChE Symp.
    Series, 87(284), 44-57 (1991)
    56. A. F. M. Barton, “Chapter 2 in handbook of Solubility Parameters and Other
    Cohesion Parameter”, 2nd ed, CRC Press, USA, 1991, pp.69-149
    57. J. W. Mullin, “Solution and solubility,” Chapter 3 of Crystallization, 3rd ed,
    (Butterworth-Heinemann, London, Great Britain, 1992), pp.93-94
    Chapter 4
    1. D. Giron, “Thermal analysis and calorimetric methods in the characterisation of
    polymorphs and solvates,” Thermochem. Acta, 248(2), l-59 (1995)
    2. E.L. P. Lee, A.O. Perez, and I. F. Tapia, “Sugar (sucrose) holograms,” Opt.
    Mater., 26(1), 5-10 (2004)
    3. P. Honig, “Physical properties of sucrose,” Chapter 2 of Principle of sugar
    technology, (Technical Research Director West Indies Sugar Corporation, 1st Ed.,
    New York, 1965), pp24-25
    4. B.I.M. Grimsey, and T. M. Herrington, “The formation of inclusions in sucrose
    crystals,” Int. Sugar J., 96(1152), 504-514 (1994)
    5. G.. Eggleston, B. J. Trask-Morrell, and J. R. Vercellotti, “Use of differential
    scanning calorimetry and thermogravimetric analysis to characterize the thermal
    degradation of crystalline sucrose and dried sucrose-salt residues,” J. Agric.
    Food Chem., 44(10), 3319-3325 (1996)
    6. S. A. Margolis, “Amperometric measurement of moisture in transformer oil
    using Karl Fischer reagents,” Anal. Chem., 67(23), 4239-4246 (1995)
    7. N. Blagden, R. J. Davey, H. F. Lieberman, L. William, R. Payne, R. Roberts, R.
    Rowe, and R. Docherty, “Crystal chemistry and solvent effects in polymorphic
    systems sulfathiazole,” J. Chem. Soc., Faraday Trans., 94(8), 1035-1044 (1998)
    8. M. Lahav, and L. Leiserowitz, “The effect of solvent on crystal growth and
    morphology,” Chem. Eng. Sci., 56(7), 2245-2253 (2001)
    9. M. Okuno, S. Kishihara, M. Otsuka, S. Fujill, and K. Kawasaki, “Variability of
    melting behavior of commercial granulated sugar measured by differential
    scanning calorimetry,” Int. S. J., 105(1249), 29-35 (2003)
    10. M. Hurtta, I. Pitkanen, and J. Knuutinen, “Melting behaviour of D-sucrose,
    D-glucose and D-fructose,” Carbo. Res., 339(13), 2267–2273 (2004)
    11. S. T. Beckett, M. G. Francesconi, P. M. Geary, G. Mackenziea, and A. P. E.
    Maulny, “DSC study of sucrose melting,” Carbo. Res., 341(15), 2591–2599
    (2006)
    12. M. L. P. Leitao, J.Canotilho, M. S. C.Cruz, J. C. Pereira, A.T. Sousa, and J. S.
    Redinha, “Study of polymorphism from DSC melting curves,” J. Therm. Anal.
    Calorim., 68(2), 397-412 (2002)
    13. C. McGregor, M. H. Saunders, G. Buckton, and R. D. Saklatvala, “The use of
    high-speed differential scanning calorimetry (Hyper-DSCTM) to study the
    thermal properties of carbamazepine polymorphs,” Thermochim. Act., 417(2),
    231–237 (2004)
    14. R. Hilfiker, “Characterization of polymorphic systems using thermal analysis,”
    Chapter 3 of Polymorphism, (In the pharmaceutical industry, 1st Ed., Weinheim,
    2006), pp71
    15. C. Mao, R. Pinal, and K. R. Morris, “A quantitative model to evaluate solubility
    relationship of polymorphs from their thermal properties,” Pharm. Res., 22(7),
    1149-1157 (2005)
    16. P.T Cardew, and R. J. Davey, “The kinetics of solvent-mediated phase transformation,” Math. Phys. Sci., 398(1815), 415-428 (1985)
    17. K. Sato, “Polymorphic transformations in crystal growth,” J. Phys. D Awl. Phys.,
    26(8), B77-84 (1993)
    18. K. Pack, J. M. B. Evans, and A. S. Myerson, “Determination of solubility of
    polymorphs using differential scanning calorimetry,” Cryst. Growth Des., 3(6),
    991-995 (2003)
    19. S. Mccarthy, and J.Billingsley, “A sensor for the sugar cane harvester topper,”
    Sen. Rev., 22(3), 242-246 (2002)
    20. H.S. Lu, H. R.Xu, Y.B. Ying, X. P. Fu, H. Y. Yu, and H. Q. Tian, “Application
    fourier transform near infrared spectrometer in rapid estimation of soluble solid
    content of intact citrus fruits,” J. Z. Univ. Sci. B 7(10), 794-799 (2006)
    21. D. K. Kondepudi, and K. E. Crook, “Theory of conglomerate crystallization in
    the presence of chiral impurities,” Cryst. Growth Des., 5(6), 2173-2179 (2005)
    22. B. Rodrıguez-Spong, C. P. Price, A. Jayasankar, A. J. Matzger, and N.
    Rodrıguez-Hornedo, “General principles of pharmaceutical solid polymorphism:
    a supramolecular perspective,” Advanced Drug Del Rev., 56(2), 241– 274 (2004)
    23. J. W. Mullin, “Crystallization techniques and equipment,” Chapter 7 of
    Crystallization, 3rd ed, (Butterworth-Heinemann, London, Great Britain,1992),
    pp.288-290
    24. S. R. Byrn, P. A. Sutton, B. Tobias, J. Frye, and P. Main, “The crystal structure,
    solid-state nmr spectra, and oxygen reactivity of five crystal forms of
    prednisolone tert-butylacetate,” J. Am. Chem. Soc., 110(5), 1609-1614 (1988)
    25. D.C. Apperley, R. A. Fletton, R. K. Harris, R. W. Lancaster, S. Tavener, and T. L.
    Threlfall, “Sulfathiazole polymorphism studied by magnetic-angle spinning
    nmr,” J. Pharm. Sci., 88(12), 1275-1280 (1999)
    26. U. R. Desai, I. R. Vlahov, A. Pervin, and R. J. Linhardt, “Conformational
    analysis of sucrose octasulfate by high resolution nuclear magnetic resonance
    spectroscopy,” Carbo. Res., 275(2), 391-401 (1995)
    27. N. Y. Park, N. I. Baek. J. Cha, S.B. Lee, J. H. Auhe, and C. S. Park, “Production
    of a new sucrose derivative by transglycosylation of recombinant sulfolobus
    shibatae b-glycosidase,” Carbo. Res., 340(66), 1089–1096 (2005)
    28. T. J. Offerdahl, “Solid-state nuclear magnetic resonance spectroscopy for
    analyzing polymorphic drug forms and formulations,” Pharm. Tech., 28, 1-11(2006)
    29. L. R. Chen, B. E. Padden, S. R. Vippagunta, E. J. Munson, and D. J. W. Grant,
    “Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil
    hydrates,” Pharm. Res., 17(5), 619-624 (2000)
    30. S. R. Byrn, G. Gary, R. R. Pfeiffer, and J. Frye, “Analysis of solid-state
    carbon-13 nmr spectra of polymorph (benoxaprofen and nabilone ) and
    pseudopolymorphs (Cefazolin),” J. Pharm. Sci., 74(5), 565-568 (1985)
    31. A. Terol, G. Cassanas, J. Nurit, B. Pauvert, A. Bouassab, J. Rambadu, and P.
    Chevallet, “Infrared, raman, and 13C nmr spectra of two crystalline forms of (1R,
    3S)-3-(p-Thioanisoyl)-1,2,2-trimethylcyclopentanecarbohylic acid,” J. Pharm.
    Sci., 83(10), 1437-1442 (1994)
    32. R. Hilfiker, “Solid-state spectroscopy,” Chapter 4 of Polymorphism, (In the
    pharmaceutical industry, 1st Ed, Weinheim, 2006), pp82-84
    33. B. E. Padden, M. T. Zell, Z. Dong, S. A. Schroeder, D. J. W. Grant, and E.J.
    Munson, “Comparison of solid-state 13C nmr spectroscopy and powder x-ray
    diffraction for analyzing mixtures of polymorphs of neotame,” Anal. Chem.,
    71(16), 3325-3331 (1999)
    34. M. Sezlagiewicz, C. Marcolli, S. Cianferani, A. P. Hard, A. Vit, A. Burkhard,
    M.von Raumer, U. Ch. Hofmeier, A. Zilian, E. Francotte, and R. Schenker, “ In
    situ characterization of polymorphic forms,” J. Therm. Anal. and Calor., 57(1),
    23-43 (1999)
    35. D. J. Sandman, L. Li, and S. Tripathy, “Conformational polymorphism of Di
    (2-naphthyl) ditelluride,” Organomet., 13(1), 348-353 (1994)
    36. T. C. Huang, “Automatic x-ray single crystal structure analysis system for small
    molecule,” The Rigaku J., 21(2), 43-46 (2004)
    37. L. Yu, S. M. Reutzel, and G. A. Stephenson, “Physical characterization of
    polymorphic drugs: an integrated characterization strategy,” PSTT 1(3), 118-127
    (1998)
    38. P. Honig, “Physical properties of sucrose,” Chapter 2 of Principle of sugar
    technology, 1st ed, (Technical Research Director West Indies Sugar Corporation,
    USA, New York, 1965), pp21-22
    39. M. Darder, and E. Ruiz-Hitzky, “Caramel-clay nanocomposites,” J. Mater.
    Chem., 15(9), 3913-3918 (2005)
    40. A. L. Cholli, and J. L. Koenig, “Spectroscopic study of the structure of sucrose in
    the amorphous the state and in aqueous solution,” Carbo. Res., 147(1-2),1-9
    (1986)
    41. C. H. Penhoat, A. Imberty, J. N. Roques, V. Michon, J. Mentech, G. Descotes,
    and S. Perez, “Conformational behavior of sucrose and its deoxy analogue in
    water as determined by nmr and molecular modeling,” J. Am. Chem. SOC.,
    11(39), 3720-3727 (1991)
    42. P. Chinachooti, and M. P. Steinberg, “Crystallinity of sucrose by x-ray diffraction
    as influenced by absorption versus desorption, waxy maize starch content, and
    water activity,” J. Food Sci., 51(2), 456-459 (1986)
    43. H.Gloria, and D. Sievert, “Changes in the physical state of sucrose during dark
    chocolate processing,” J.Agric. Food Chem., 49(5), 2443-2436 (2001)
    44. J. C. Hanson, L. C. Sieker, and L. H. Jensen, “Sucrose: x-ray refinement and
    comparision with neutron refinement,” Acta. Cryst., B29, 797-808 (1973)
    45. R. Hilfiker, “Characterization of polymorphic systems using thermal analysis,”
    Chapter 3 of Polymorphism, (In the pharmaceutical industry, 1st Ed., Weinheim,
    2006), pp72
    Chapter 5
    1. J. E. Botzolakis, and L. L. Augsburger, “The role of distintegrants in hard-gelatin
    capsules,” J. Pharm. Pharmacol., 36(2), 77-84 (1984)
    2. C. R. Chen, Y. H. Lin, S. L. Cho, S. H. Yen, and H. L. S. Wu, “ Investigation of
    the dissolution difference acidic and neutral media of acetaminophen tables
    containing a super distintegrant and a soluble excipient,” Chem. Pharm. Bull.,
    45(3), 509-512 (1997)
    3. A. A. Joshi, and X. Duriez, “ Added functionality excipients: An answer to
    challenging formulations,” Pharm. Tech., 12, 12-19 (2004)
    4. C. R. Chen, S. L. Cho, Y. H. Lin, S. H. Yen, and H. L. S. Wu, “ Investigation of
    the dissolution difference acidic and neutral media of acetaminophen tables
    containing a super distintegrant and a soluble excipient,” Chem. Pharm. Bull.,
    46(3), 478-481 (1998)
    5. G. K. bolhuis, and Z. T. Chowhan, “ Materials of direct compaction,” Pharm.
    Powder Compaction Tech., 71(14), 419-500 (1996)
    6. M. C. Gohel, and B. S. D. Marg, “A review of co-processed directly
    compressible excipients,” J. Pharm. Pharmaceut. Sci., 8(1), 76-93 (2005)
    7. M. A. Goshko, W. O. Pipes, and R. R. Christian, “Possible confusion between
    enterobacter agglomerans and Escherichia coli,” Pharm. Tech., 8, 32-39 (1984)
    8. S. A. Sangekar, M. Sarli, and P. R. Sheth, “Effect of moisture on physical
    characteristics of tables prepared from direct compression excipients,” J. Pharm. Sci., 61(6), 939-944 (1972)
    9. J. W. D. Ross, “Modification of the crystalline structure of sorbitol and its effect
    tableting characteristics,” Pharm. Tech., 8, 42-53 (1984)
    10. M. S. Gordon, V. S. Rudraraju, K. Dani, and Z. T. Chowhan, “Effect of the mode
    of super distintegrant incorporation on dissolution in wet granulated tables,” J.
    Pharm. Sci., 82(2), 220-224 (1993)
    11. M. S. Gorden, V. S. Rudraraju, J. K. Rhie, and Z. T. Chowhan, “The effect of
    aging on the dissolution of wet granulated tables containing super disintegrants,”
    Int. J. Pharm., 97(1-3), 119-131 (1993)
    12. A. Wade, and P. J. Weller, “Sucrose,” Handbook of pharmaceutical excipients,
    2nd ed, (American Pharmaceutical Association, Washington, USA, 1994),
    pp.500-505
    13. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar
    technology ,1st ed, Technical Research Director West Indies Sugar Corporation,
    New York, USA, 1965, pp24-25
    14. P. Honig, “Chemical properties of sucrose,” Chapter 1 of Principle of sugar
    technology , 1st ed, Technical Research Director West Indies Sugar Corporation,
    New York, USA, 1965, pp22
    15. J. McMurry, “Biomolecules: Carbohydrates,” Chapter 25 of Organic Chemistry,
    (Thomson Learning, Inc., Belmont, USA, 2004), p. 969
    16. M. Sugimoto, T. Maejima, S. Narisawa, K. Matsubara, and H. Yoshino, “Factors
    affecting the characteristics of rapidly disintegrating tables in the mouth prepared
    by crystalline transition of amorphous sucrose,” Int. J. Pharm., 296(1-2), 64-72
    (2005)
    17. A. Wade, and P. J. Weller, “Sucrose,” Handbook of pharmaceutical excipients,
    2nd ed, American Pharmaceutical Association, Washington, USA, 1994,
    pp.502-503
    18. S. L. Wang, S. Y. Lin, and Y. S. Wei, “Transformation of Metastable Forms of
    Acetaminophen Studied by Thermal Fourier Transform Infrared(FT-IR)
    Microspectroscopy,” Chem. Pharm. Bull., 50(2), 153-156 (2002)
    19. B. A. Hendriksen, and D. J. W. Grant, “The effect of structurally related
    substances on the nucleation kinetics of paracetamol (acetaminophen),” J. Cry.
    Grow., 156(3), 252-260 (1995)
    20. R. I. Ristic, S. Finnie, D. B. Sheen, and J. n. Sherwood, “Macro-and
    micromorphology of monoclinic paracetamol grown from pure aqueous
    solution,” J. Phys. Chem. B, 105(38), 9057-9066 (2001)
    21. B. Albertini, C. Cavallari, N. Passerini, D. Voinovich, M. L. G. Rodriguez, L. Magarotto, and L. Rodriguez, “Characterization and test-masking evaluation of
    acetaminophen granulates: comparison between different preparation methods in
    a high-shear mixer,” Europ. J. Pharm. Sci., 21(2-3), 295-303 (2004)
    22. D. J. V. Drooge, W. L. J. Hinrichs, and H. W. Frijlink, “Anomalus dissolution
    behavior of tables prepared from sugar glass-based solid dispersions,” J.
    Controlled Release., 97(3), 441-452 (2004)
    23. E. B.Vadas, G. R. B. Down, and R. A. Miller, “Effect compression force on tables
    containing cellulosic disintegrators Ⅰ: dimensionless disintegration values,” J.
    Pharm. Sci., 73(6), 781-783 (1984)
    24. J. E. Botzolakis, and L. L. Augsburger, “Disintegrating agent in hard gelatin
    capsules. Part Ⅱ: swelling efficiency,” Drug Dev. Ind. Pharm., 14(9), 1235-1248
    (1998)
    25. S. Kim, B. Lotz, M. Lindrud, K. Girard, T. Moore, K. Nagarajan, M. Alvarez, T.
    Lee, F. Nikfar, M. Davidovich, S. Srivastava and S. Kiang, “Control of the
    particle properties of a drug substance by crystallizatioin engineering and the
    effect on drug Product Formulatioin,” Org. Process Res. Dev., 9(6), 894-901
    (2005)
    26. M. Charoenchaitrakool, F. Dehghani, and N. R. Foster, “Micronization by rapid
    expansioin of supercritical solutions to enhance the dissolution rates of poorly
    water-soluble pharmaceuticals,” Ind. Eng. Chem. Res., 39(12), 4794-4802 (2000)
    27. A. P. Tinke, K. Vanhoutte, R. Ed Maesschalck, S. Verheyen, and H. De Winter,
    “A new approach in the prediction of the dissolution behavior of suspended
    particles by means of their particle size distribution,” J. Pharm. Bio. Ana., 39(5),
    900-907 (2005)
    28. J. Hecq, M. Dellers, D. Fanara, H. Vranckx, and K. Amighi, “Prepareation and
    characterization of nanocrystals for solubility and dissolution rate enhancement
    of nifedipine,” Int. J. Pharm., 299(1-2), 167-177 (2005)
    29. G. G. Liversidge, and K. C. Cundy, “Particle size reduction for improvement of
    oral bioavailability of hydrophobic drugs: I. absolute oral bioavailability of
    nanocrystalline danazol in beagle dogs,” Int. J. Pharm., 125(1), 91-97 (1995)
    30. B. Y. Shekunov, P. Chattopadhyay, J. Seitzinger, and R. Huff, “Nanoparticles of
    poorly water-soluble drugs prepared by supercritical fluid extraction of
    emulsions,” Pharm. Res., 23(1), 196-204 (2006)
    31. M. Mosharraf, and C. Nyström, “The effect of particle size and shape on the
    surface specific dissolution rate of microsized practically insoluble drugs,” Int. J.
    Pharm., 122(1-2), 35-47 (1995)
    32. W. J. Genck, “Optimizing crystallizer scaleup: understand the impact of mixing
    on crystallization dynamics and determine the optimum conditions for scale-up,”
    AIChE, 99(6), 36-44 (2003)
    33. T. Lee, and J. Lee, “Particle attrition by particle-surface friction in dryers,”
    Pharm. Tech. North America, 27(5), 64-72 (2003)
    34. S. A. Altaf, S. W. Hoag, and J. W. Ayres, “Bead compacts II evaluation of rapidly
    disintegrating nonsegregating compressed bead formulations,” Drug Dev. Ind.
    Pharm., 25(5), 635-642 (1999)
    35. N. K. Ebube, A. H. Hikal, C. M. Wyandt, D. C. Beer, L. G. Miller, and A. B.
    Jones “Effect of drug formulation and process variables on granulation and
    compaction characteristics of heterogeneous matrices. Part 1: HPMC and HPC
    systems,” Int. J. Pharm., 156(1), 49-57 (1997)
    36. M. J. Habib, “Pharmaceutical solid dispersion technology,” Technomic
    Publishing Company, Inc., Pennsylvania, USA, 2001, pp. 12

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