探察混合對苯甲酸-苯甲酸鈉共晶體所形成的化學計量之效應

簡易檢索 / 詳目顯示

回結果列表

研究生：	陳子軒 Tzu-Hsuan Chen
論文名稱：	探察混合對苯甲酸-苯甲酸鈉共晶體所形成的化學計量之效應 Investigating Mixing Effect on Stoichiometric Ratios Diversity of Benzoic Acid-Sodium Benzoate Co-crystals
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
論文出版年：	2018
畢業學年度：	106
語文別：	英文
論文頁數：	94
中文關鍵詞：	共晶、混合、化學計量數
外文關鍵詞：	Co-crystals, Mixing, Stoichiometric ratio
相關次數：	點閱：9 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

共晶提供了一個良好的機會來提高藥物的物理化學性質，如熔點、溶解度、穩定性、生物利用度和滲透度。我們的目標是探討混合效應對苯甲酸-苯甲酸鈉共晶體的化學計量數的影響。將8 mL 濃度3.36 M的鹽酸水溶液以3.5或20 mL/min的速率在75或600 rpm的攪拌速率下加入到攪拌槽中，並與192 mL 濃度1.74 M的苯甲酸鈉水溶液反應形成苯甲酸，苯甲酸與苯甲酸鈉結晶得到其共晶。微觀混合和巨觀混合是由攪拌葉片的攪拌速率所造成的，而介混合是由鹽酸水溶液的進料速率所造成的。透過熱重分析儀(TGA)， X射線粉末繞射儀(PXRD)和光學顯微鏡(OM)檢測其化學計量、晶體結構和晶貌。攪拌速率和鹽酸水溶液的進料速率可能影響苯甲酸-苯甲酸鈉共晶的組成。隨著混合強度的增加和鹽酸水溶液的進料速率的降低，進料口的苯甲酸局部濃度降低。反之，隨著混合強度的降低和鹽酸水溶液的進料速率的增加，進料口的苯甲酸的局部濃度增加。介混合對苯甲酸-苯甲酸鈉共晶組成的影響在75 rpm下可被觀察。苯甲酸-苯甲酸鈉的Form A 2：1共晶僅在75 rpm以及3.36 M鹽酸水溶液進料速率20 mL/min時間為20分鐘時獲得。Form B 2:1的苯甲酸-苯甲酸鈉共晶並沒有被檢測到。無論在75 rpm或600 rpm以及3.5或20 mL/min的鹽酸水溶液的進料速率下，如果予以充足的時間，固體皆會轉化為1：1和2：1苯甲酸-苯甲酸鈉共晶的混合物。此外，還進行了攪拌速率和鹽酸水溶液進料速率的極端條件的實驗。以600 rpm和0.4 mL/min濃度3.36 M的鹽酸水溶液的進料速率，在10分鐘時獲得苯甲酸-苯甲酸鈉的1：1共晶。攪拌速率也影響了粒徑分佈，由於晶體磨損和破裂，在高攪拌速率下粒徑分佈也隨之減少。

Co-crystallization offers a great opportunity to enhance the physicochemical properties of drug products, such as melting point, solubility, stability, bioavailability and permeability. Our aim was to probe the mixing effect on the stoichiometry diversity of benzoic acid-sodium benzoate (HBz-NaBz) co-crystals. 8 mL of 3.36 M hydrochloric acid were fed with a rate of 3.5 or 20 mL/min into the agitated tank having the agitation rate of 75 or 600 rpm and reacted with 192 mL of the 1.74 M aqueous solution of sodium benzoate to form benzoic acid, and benzoic acid was then co-crystallized with sodium benzoate to give the co-crystals of HBz-NaBz. Micromixing and macromixing were contributed by the agitation rate of a propeller, and mesomixing was originated by the feeding rate of HCl(aq). The stoichiometric ratios, crystal structures, and crystal habit of solids were characterized by thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and optical microscopy (OM). The agitation rate and the feeding rate of HCl(aq) could influence the compositions of HBz-NaBz co-crystals. The local concentration of benzoic acid at the feeding point was decreased with the increase in the mixing intensity and the decrease in the feeding rate of HCl(aq). By contrast, the local concentration of benzoic acid at the feeding point was increased with the decrease in the mixing intensity and the increase in the feeding rate of HCl(aq). The effect of mesomixing on the compositions of HBz-NaBz co-crystals could be observed under 75 rpm. Pure Form A 2:1 co-crystals of HBz-NaBz were only obtained at 75 rpm and with a feeding rate of 3.36 M HCl(aq) of 20 mL/min at 20 min. Form B 2:1 co-crystals of HBz-NaBz were not detected at all. Finally, the solids were transformed to the mixtures of 1:1 and 2:1 co-crystals of HBz-NaBz at 75 rpm or 600 rpm and the feeding rate of 3.36 M HCl(aq) of 3.5 or 20 ml/min if given a long enough time. In addition, the extreme conditions for the agitation rate of propeller and the feeding rate of HCl(aq) were carried out. Pure 1:1 co-crystals of HBz-NaBz were obtained at 600 rpm and 0.4 mL/min with a feeding rate of 3.36 M HCl(aq) of 0.4 mL/min at 10 min. Agitation rate had also influenced the particle size distribution (PSD), and the PSD decreased under a high agitation rate due to crystal attrition and breakage.

Table of Contents
摘要    i
Abstract    ii
Acknowledgement    iv
Table of Contents    v
List of Figures    viii
List of Tables    xiii
List of Schemes    xiv
Chapter 1    Introduction    1
1.1    Micromixing, Mesomixing, and Macromixing    1
1.2    Mixing in Reaction Crystallization    3
1.3    Co-crystals    4
1.4    HBz, NaBz, and 1:1 and 2:1 Co-crystals of HBz-NaBz    5
1.5    Framework    9
1.6    References    11
Chapter 2    Experimental Materials and Methods    15
2.1    Materials    15
2.1.1    Chemical    15
2.1.2    Solvent    15
2.2    Experimental Procedures    15
2.2.1    Synthesizing 2:1 Co-crystals of Benzoic Acid-Sodium Benzoate (HBz-NaBz) by Cooling Method    15
2.2.2    The Study of Synthesizing Co-crystals of Benzoic Acid-Sodium Benzoate (HBz-NaBz) by adding Hydrochloric Acid    17
2.2.3    The Study of Different Scales of Mixing Effect to Co-crystals of HBz-NaBz by Feeing Hydrochloric Acid in the Stirred Vessel    20
2.2.4    Extreme Mixing Conditions for the HBz-NaBz Co-crystals Formation    23
2.2.5    Wet Sieve Analysis Method    25
2.3    Analytical Measurements    26
2.3.1    Powder X-ray Diffraction (PXRD)    26
2.3.2    Fourier Transform Infrared (FTIR) Spectroscopy    27
2.3.3    Thermal Gravimetric Analysis (TGA)    28
2.3.4    Optical Microscopy (OM)    28
2.4    References    30
Chapter 3    Results and Discussion    31
3.1    Use Tests    31
3.2    Synthesizing Co-crystals by Different Molar Ratios of NaBz to HCl    36
3.3    Different Scales of Mixing Effect on the HBz-NaBz Co-crystals    41
3.3.1    The Study of Different Scales of Mixing Effect to the HBz-NaBz Co-crystals According to Table 2.2    42
3.3.2    Extreme Mixing Conditions for the HBz-NaBz Co-crystals Formation According to Table 2.3    58
3.3.3    Particle Size Distribution    65
3.4    References    69
Chapter 4    Conclusions and Future Works    71
4.1    Conclusions    71
4.2    Future Works    73
4.3    References    74

 
List of Figures
Figure 1.1  Crystalline form of co-crystal.    4
Figure 1.2  Crystal structure of NaBz (a) Form I, and (b) Form II.    6
Figure 1.3  Crystal structure of 2:1 co-crystals of HBz-NaBz (a) Form A, and (b) Form B.    8
Figure 2.1  The process of synthesizing 2:1 co-crystals of HBz-NaBz.    16
Figure 2.2  The process of synthesizing co-crystals of HBz-NaBz.    17
Figure 2.3  The dimension of propeller and reactor.    20
Figure 2.4  The process of synthesizing co-crystals of HBz-NaBz in the stirred reactor.    22
Figure 2.5  The process of synthesizing HBz-NaBz co-crystals in a stirred reactor.    24
Figure 2.6  Powder X-ray diffraction (PXRD).    26
Figure 2.7  Fourier transform infrared (FT-IR) spectroscopy.    27
Figure 2.8  Thermal gravimetric analyzer (TGA).    28
Figure 2.9  Optical microscopy.    29
Figure 3.1  PXRD Patterns of the purchased (a) NaBz, and (b) HBz, the synthesized (c) 1:1 co-crystals of HBz-NaBz, and (d) 2:1 co-crystals of HBz-NaBz (◆ NaBz,○ 1:1 co-crystals of HBz-NaBz, ● 2:1 co-crystals of HBz-NaBz, and ✽ HBz).-    31
Figure 3.2  FTIR spectra of the purchased (a) NaBz, (b) HBz, the synthesized (c) 2:1    32
Figure 3.3  TGA scan of NaBz.    33
Figure 3.4  TGA scan of HBz.    33
Figure 3.5  TGA scan of 1:1 co-crytals of HBz-NaBz.    34
Figure 3.6  TGA scan of 2:1 co-crytals of HBz-NaBz.    34
Figure 3.7  TGA scans of (a) Experiment No.1, (b) Experiment No. 2, (c) Experiment No. 3, (d) Experiment No. 4, (e) Experiment No. 5, and (f) Experiment No. 6 based on Table 2.1.    37
Figure 3.8  PXRD patterns of (a) Experiment No.1, (b) Experiment No. 2, (c) Experiment No. 3, (d) Experiment No. 4, (e) Experiment No. 5, and (f) Experiment No. 6 based on Table 2.1 (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    37
Figure 3.9  OM images of (a) Experiment No.1, (b) Experiment No. 2, (c) Experiment No. 3, (d) Experiment No. 4, (e) Experiment No. 5, and (f) Experiment No. 6 based on Table 2.1 (scale bar = 200 μm).    38
Figure 3.10  TGA scans of the samples harvested in Experiment No. 7 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min.    43
Figure 3.11  PXRD patterns of the samples harvested in Experiment No. 7 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    43
Figure 3.12  OM images of the samples harvested in Experiment No. 7 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (scale bar = 200 μm).    44
Figure 3.13  TGA scans of the samples harvested in Experiment No. 8 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min.    46
Figure 3.14  PXRD patterns of the samples harvested in Experiment No. 8 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    46
Figure 3.15  OM images of the samples harvested in Experiment No. 8 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (scale bar = 200 μm).    47
Figure 3.16  TGA scans of the samples harvested in Experiment No. 9 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min.    49
Figure 3.17  PXRD patterns of the samples harvested in Experiment No. 9 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    50
Figure 3.18  OM images of the samples harvested in Experiment No. 9 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (scale bar = 200 μm).    51
Figure 3.19  TGA scans of the samples harvested in Experiment No. 10 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min.    53
Figure 3.20  PXRD patterns of the samples harvested in Experiment No. 10 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    53
Figure 3.21  OM images of the samples harvested in Experiment No. 10 based on Table 2.2 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (scale bar = 200 μm).    54
Figure 3.22  The mixing effect on the evolution of co-crystals of HBz-NaBz.    57
Figure 3.23  TGA scans of the samples harvested in Experiment No. 11 based on Table 2.3 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min.    59
Figure 3.24  PXRD patterns of the samples harvested in Experiment No. 11 based on Table 2.3 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    59
Figure 3.25  OM images of the samples harvested in Experiment No. 11 based on Table 2.3 at (a) 1 min, (b) 3 min, (c) 5 min, (d) 10 min, (e) 20 min, (f) 30 min, and (g) 240 min (scale bar = 200 μm).    60
Figure 3.26  TGA scans of the samples harvested in Experiment No. 12 based on Table 2.3 at (a) 10 min, (b) 20 min, (c) 30 min, and (d) 240 min.    62
Figure 3.27  PXRD patterns of the samples harvested in Experiment No. 12 based on Table 2.3 at (a) 10 min, (b) 20 min, (c) 30 min, and (d) 240 min (✽ HBz, ○ 1:1 co-crystals of HBz-NaBz, and ● 2:1 co-crystals of HBz-NaBz).    62
Figure 3.28  OM images of the samples harvested in Experiment No. 12 based on Table 2.3 at (a) 10 min, (b) 20 min, (c) 30 min, and (d) 240 min (scale bar = 200 μm).    63
Figure 3.29  The pathway of crystal formation based on Experiment No. 12.    64
Figure 3.30  The crystal size distribution on each sieve plate of co-crystals of HBz-NaBz produced from (a) Experiment No. 7, (b) Experiment No. 8, (c) Experiment No. 9, (d) Experiment No. 10 based on Table 2.2 at 240 min.    66
Figure 3.31  The dissolution rate and re-crystallization rate based on film theory at (a) low flow rate, and (b) high flow rate.    67
Figure 4.1  The flow diagram of scale up of reactor.    73
 
List of Tables 
Table 1.1  The crystallographic data for Form I and Form II of NaBz.    6
Table 1.2  The crystallographic data for Form A and Form B of 2:1 co-crystals of HBz-NaBz.    8
Table 2.1  Experimental conditions for the formation of co-crystals of HBz-NaBz in different molar ratios of NaBz to HCl.    19
Table 2.2  Experimental conditions for the formation of co-crystals of HBz-NaBz in the stirred reactor under different agitation rates and feeding rates.    22
Table 2.3  Two experimental conditions for the formation of HBz-NaBz co-crystals.    24
Table 3.1  The calculation of weight (%) of HBz and NaBz in the co-crystals system.    35
Table 3.2  The results of the synthesized co-crystals by different molar ratios of NaBz to HCl.    40

 
List of Schemes
Scheme 2.1  The pathway of reaction of sodium benzoate with hydrochloric acid.    17
Scheme 2.2  The chemistry of synthesizing co-crystals of HBz-NaBz.    20



                                

Chapter 1.
1. Danckwerts, P. V. The Effect of Incomplete Mixing on Homogeneous Reactions. Chem. Eng. Sci. 1958, 8 (1-2), 93-102.
2. Jones, A. G. Crystallization Process System, 1st ed.; Butterworth-Heinemann: Oxford, OFE, 2002; pp. 49.
3. Boodhoo, K.; Harvey, A. Process Intensification: An Overview of Principles and Practice, 1st ed.; John Wiley & Sons: Hoboken, NJ, 2013; pp. 12.
4. Baldyga, J.; Bourne, J. R. Interactions between Mixing on Various Scales in Stirred Tank Reactors. Chem. Eng. Sci. 1992, 47 (8), 1839-1848.
5. Baldyga. J.; Podgorska, W.; Pohorecki, R. Mixing-Preccipitation Model with Application to Double Feed Semibatch Precipitation. Chem. Eng. Sci. 1995, 50 (8), 1281-1300.
6. Torbacke, M.; Rasmuson, Å. C. Influence of Different Scales of Mixing in Reaction Crystallization. Chem. Eng. Sci. 2001, 56 (7), 2459-2473.
7. Åslund, B.; Rasmuson, Å. Semibatch Reaction Crystallization of Benzoic Acid. AlChE J. 1992, 38 (3), 328-342.
8. Aakeröy, C. B.; Forbes, S.; Desper, J. Using Cocrystals to Systematically Modulate Aqueous Solubility and Melting Behavior of an Anticancer Drug. J. Am. Chem. Soc. 2009, 131 (47), 17048-17049.
9. Blagden, N.; De Matas, M.; Gavan, P. T.; York, P. Crystal Engineering of Active Pharmaceutical Ingredients to Improve Solubility and Dissolution Rates. Adv. Drug. Deliv. Rev. 2007, 59 (7), 617-630.
10. Hickey, M. B.; Peterson, M. L.; Scoppettuolo, L. A.; Morrisette, S. L.; Vetter, A. Performance Comparison of a Co-crystal of Carbamazepine with Marketed Product. Eur. J. Pharm. Biopharm. 2007, 67 (1), 112-119.
11. McNamara, D. P.; Childs, S. L.; Giordano, J.; Iarriccio, A.; Cassidy, J.; Shet, M. S.; Mannion, R.; Park, A. Use of a Glutaric Acid Cocrystal to Improve Oral Bioavailability of a Low Solubility API. Pharm. Res. 2006, 23 (8), 1888-1897.
12. Thakuria, R.; Delori, A.; Jones, W.; Lipert, M.P.; Roy. L.; Rodríguez-Hornedo, N. Pharmaceutical Cocrystals and Poorly Soluble Drugs. Int. J. Pharm. 2013, 453 (1), 101-125.
13. Bethune, S. J.; Schultheiss, N.; Henck, J. O. Improving the Poor Aqueous Solubility of Nutraceutical Compound Pterostilbene through Cocrystal Formation. Cryst. Growth Des. 2011, 11 (7), 2817-2823.
14. Zhang, J.; Geng, H.; Virk, T. S.; Zhao, Y.; Tan, J.; Di, C. A.; Xu, W.; Singh, K.; Hu, W.; Shuai, Z.; Liu, Y.; Zhu, D. Sulfur-Bridged Annulene-TCNQ Co-crystal: A Self-Assembled “Molecular Level Heterojunction” with Air Stable Ambipolar Charge Transport Behavior. Adv. Mater. 2012, 24 (19), 2603-2607.

15. Spitzer, D.; Risse, B.; Schnell, F.; Pichot, V.; Continuous Engineering of Nano-Cocrystals for Medical and Energetic Applications. Sci. Rep. 2014, 4 (6575), 1-6.
16. Davidson, M. P.; Sofos, J. N.; Baranen, A. L. Antimicrobials in Food, 3rd ed.; CRC Press: Boca Raton, FL, 2005; pp. 11.
17. Breitkreutz, J.; Bornhöft, M.; Wöll, F.; Kleinebudde, P. Pediatric Drug Formulations of Sodium Benzoate: I. Coated Granules with a Hydrophilic Binder. Eur. J. Pharm. Biopharm. 2003, 56 (2), 247-253.
18. Butterhof, C.; Martin, T.; Milius, W.; Breu, J. Microphase Separation with Small Amphiphilic Molecules: Crystal Structure of Preservatives Sodium Benzoate (E 211) and Potassium Benzoate (E 212). Anorg. Allg. Chem. 2013, 639 (15), 2816-2821.
19. Martin, T. W.; Gorelik, T. E.; Greim, D.; Butterhof, C.; Kolb, U.; Senker, J.; Breu, J.; Microphase Separation upon Crystallization of Small Amphilic Molecules: “Low” Temperature Form II of Sodium Benzoate (E 211). CrystEngComm 2016, 18 (31), 5811-5817.
20. Brittain, H. G. Vibrational Spectroscopic Studies of Cocrystals and Salts. 3. Cocrystal Products Formed by Benzenecarboxylic Acids and Their Sodium Salts. Cryst. Growth Des. 2010, 10 (4), 1990-2003.
21. Butterhof, C.; Milius, W.; Breu, J. Co-crystallization of Benzoic Acid with Sodium Benzoate: the Significance of Stoichiometry. CrysEngComm 2012, 14 (11), 3945-3950.
22. Butterhof, C.; Bärwinkel, K.; Senker, J.; Breu, J. Polymorphiam in Co-crystals: Ametastable Form of the Ionic Co-crystal 2 HBz-1 NaBz Crystallised by Flash Evaporation. CrysEngComm 2012, 14 (11), 6744-6749.
23. Lee, H. L.; Lee, T. Direct Co-crystal Assembly from Synthesis to Cocrystallization. CrystEngComm 2012, 17 (47), 8967-9624.

Chapter 2.
1. Butterhof, C.; Bärwinkel, K.; Senker, J.; Breu, J. Polymorphism in Co-crystals: A Metastable Form of the Ionic Co-crystal 2 HBz-1 NaBz Crystallised by Flash Evaporation. CrystEngComm 2012, 14 (11), 6744-6749.
2. Brittain, H. G. Vibrational Spectroscopic Studies of Cocrystals and Salts. 3. Cocrystal Products Formed by Benzenecarboxylic Acids and Their Sodium Salts. Cryst. Growth Des. 2010, 10 (4), 1990-2003.
3. Åslund, B.; Rasmuson, Å. Semibatch Reaction Crystallization of Benzoic Acid. AlChE J. 1992, 38 (3), 328-342.
4. Torbacke, M.; Rasmuson, Å. C. Influence of Different Scales of Mixing in Reaction Crystallization. Chem. Eng. Sci. 2001, 56 (7), 2459-2473.

Chapter 3.
1. Khosravan, M.; Shoshtari, A. N.; Hoseinchi, L. Synthesis of Nano Sodium Benzoate as a Food Preservative and Investigative Its Effect on Food Spoilage Bacteria. Synth. React. Inorg. Met.-Org. Chem. 2016, 46 (1), 51-54.
2. Maruyama, S. A.; Lisboa, F. S.; Ramos, L. P.; Wypych. F.; Alkaline Earth Layered Benzoates as Reusable Heterogeneous Catalysts for The Methyl Esterification of Benzoic Acid. Quim. Nova. 2012, 35 (8), 1510-1516.
3. Butterhof, C.; Bärwinkel, K.; Senker, J.; Breu, J. Polymorphism in Co-crystals: A Metastable Form of the Ionic Co-crystal 2 HBz-1 NaBz Crystallised by Flash Evaporation. CryEngComm 2012, 14 (11), 6744-6749.
4. Butterhof, C.; Miliu, W.; Breu, J. Co-crystallisation of Benzoic Acid with Sodium Benzoate: Significance of Stoichiometry. CrystEngComm 2012, 14 (11), 3945-3950.
5. Robert, R. M.; Gibert, J. C. Modern Experimental Organic Chemistry, 4thN ed.; Saunders College Publishing: Philadelphia: PA, 1985; pp. 222-223.
6. Brittan, H. G. Vibrational Spectroscopic Studies of Cocrystals and Salts. 3. Cocrystal Products Formed by Benzenecarboxylic Acids and Their Sodium Salts. Cryst. Growth Des. 2010, 10 (4), 1990-2003.
7. Baldyga, J.; Bourne, J. R. Interactions between Mixing on Various Scales in the Stirred Tank Reactors. Chem. Eng. Sci. 1992, 47 (8), 1839-1848.
8. Torbacke, M.; Rasmuson, Å. C. Influence of Different Scales of Mixing in Reaction Crystallization. Chem. Eng. Sci. 2001, 56 (7), 2459-2473.
9. Marcant, B.; David, R. Experimental Evidence for and Prediction of Micromixing Effects in Precipitation. AIChE J. 1991, 37 (11), 1698-1710.
10. Hsu, Y. C.; Lee, T. A Cross-Performance Relationship Between Carr’s Index and Dissolution Rate Constant: The Study of Acetaminophen Batches. Drug Dev. Ind. Pharm. 2007, 33 (11), 1273-1284.
11. Åslund, B.; Rasmuson, Å. Semibatch Reaction Crystallization of Benzoic Acid. AlChE J. 1992, 38 (3), 328-342.

Chapter 4.
1. Kulk, C.; Wood, C.; Gough, T.; Blagden, N.; Paradkar, A. Stoichiometric Control of Co-crystal Formation by Solvent Free Continuous Co-crystallization (SFCC). Cryst. Growth Des. 2015, 15 (12), 5648-5651.
2. Bag, P. P.; Patni, M.; Reddy, C. M. A Kinetically Controlled Crystallization Process for Identifying New Co-crystal Forms: Fast Evaporation of Solvent from Solutions to Dryness. CrystEngComm 2011, 13 (19), 5650-5652.
3. Alhalaweh, A.; Velaga, S. P. Formation of Cocrystals from Stoichiometric Solutions of Incongruently Saturating Systems by Spray Drying. Cryst. Growth Des. 2010, 10 (8), 3302-3305.

簡易檢索 / 詳目顯示

相關論文