1：1茶鹼－乙醯胺酚共晶體之機械化學合成的機制及濕粒法的化學穩定性

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曾子珉(Tzu-Min Tseng) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

1：1茶鹼－乙醯胺酚共晶體之機械化學合成的機制及濕粒法的化學穩定性
(Mechanism for Mechanochemical Synthesis and Chemical Stability for Wet Granulation of 1:1 Co-crystals of Theophylline and Acetaminophen)

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摘要(中)

共晶體是由兩種或兩種以上的分子借由非共價鍵與一定的化學劑量比所形成的結晶，共結晶是改善活性藥物成分（API）的溶解度與機械性能的方法之一，在本研究中，我們選擇茶鹼和乙醯胺酚來製備1：1茶鹼－乙醯胺酚共晶體，並通過與乙醯胺酚共結晶來提高茶鹼的溶解度和機械化學性質，我們使用三種不同方法製備1：1茶鹼－乙醯胺酚共晶體：（a）直接共晶組裝，（b）再結晶，（c）無溶劑球磨，針對不同方法製備的1：1茶鹼－乙醯胺酚共晶體的溶解速率進行了比較，此外也探討1：1茶鹼－乙醯胺酚共晶體的機械化學機理。據我們所知，已有一些研究文獻提及濕粒法和共晶體配方的溶解速率測試，在濕粒法中，水可以做為粘合劑液體。本研究發現經過濕粒法後1：1茶鹼－乙醯胺酚共晶體不會受賦形劑和粘合劑影響，證實其具有高化學穩定性，在溶解度測試中，使用符合美國藥典(USP)規定之溶出裝置 - 溶離槳式（37℃）對從不同製備方法獲得的1：1茶鹼－乙醯胺酚共晶體進行溶解試驗。儘管其他研究組已經把濕粒法與共結晶相結合，但無溶劑球磨完全是無溶劑的步驟且與濕粒法分離。本篇研究提供了五個優點：（1）共晶體形成過程可被清楚地監測，（2）沒有檢測到其他不純相，（3）茶鹼的藥物釋放速率（T50 = 3.6分鐘）可藉由與乙醯胺酚共結晶而有所提升（T50 = 2.8〜3.0分鐘），（4）濕粒法不會影響1：1茶鹼－乙醯胺酚共晶體的化學穩定性與茶鹼的藥物釋放速率（T50 = 3.8分鐘），和（5）以無溶劑球磨機方法為綠色製程，且所製備之1：1茶鹼－乙醯胺酚共晶體與其他常規溶液結晶方法製備之共晶體質量與溶解度測試結果一樣。

摘要(英)

A co-crystal is formed when the assembly of two or more distinct molecular species in a definite stoichiometric ratio occurred through the interactions of hydrogen bonds and non-covalent bonds in a long range order. Co-crystallization is a way to alter or enhance the solubility and mechanical properties of active pharmaceutical ingredient (API). In this research, acetaminophen and theophylline were chosen to generated the 1:1 co-crystal of acetaminophen-theophylline (1:1 Ace-Thy co-crystal) to enhance the solubility and mechanochemical properties of theophylline by co-crystallized with acetaminophen. The mechanism for mechanochemistry of 1:1 Ace-Thy co-crystal was also discussed. Three preparation methods for 1:1 Ace-Thy co-crystal were studied: (a) direct co-crystal assembly, (b) re-crystallization, and (c) solvent-less ball-milling. The dissolution rates of pure 1:1 Ace-Thy co-crystals prepared by different methods also be conducted and compared. To the best of our knowledge, a few studies had investigated the wet granulation and the dissolution of formulated co-crystals. In this research, USP Dissolution Apparatus – Paddle (37°C) was chosen to do the dissolution test for the formulated granules of 1:1 Ace-Thy co-crystals obtained from different preparation methods. Although co-crystallization had been integrated with high-shear and wet granulation by other research groups, co-crystallization in ball mill was completely a solvent-less step because it was separated from wet granulation. The chemical stability of 1:1 Ace-Thy co-crystals in the presence of excipients and binders was studied and verified in this research. Water could be the binder liquid, but not acetone, for wet granulation.　　Five advantages were offered: (1) co-crystal formation was clean and easy to be monitored by characterization tools, (2) no other impure phase was detected, (3) the theophylline drug release was increased (T50 = 3.6 min) by the co-crystal formation (T50 = 2.8 to 3.0 min), (4) in the presence of formulation and water, no influence of co-crystal formation (T50 = 3.5 to 3.9 min) on chemical stability or on theophylline drug release (T50 = 3.8 min), and (5) the environmentally benign solvent-less ball mill methods was as good as the other conventional solution crystallization methods in terms of the co-crystal quality and dissolution behavior of the same particle size.

關鍵字(中)

★ 共晶

關鍵字(英)

★ Co-crystal

論文目次

Table of Contents

摘要 i
Abstract ii
Acknowledgement iv
List of Figures viii
List of Tables xii
List of Schemes xiii
Chapter 1 Introduction 1
1.1 Brief Introduce of Co-crystal 1
1.2 1:1 Co-crystal of Acetaminophen-Theophylline 3
1.3 Wet Granulation 5
1.4 Conceptual Framework 6
1.5 References 8
Chapter 2 Experimental Materials and Methods 14
2.1 Materials 14
2.1.1 Chemicals 14
2.1.2 Solvents 14
2.2 Experimental Procedures 15
2.2.1 Direct Co-crystal Assembly 15
2.2.2 Re-crystallization 16
2.2.3 Solvent-less Ball-milling 17
2.2.4 Wet Granulation 18
2.2.5 Particle Size Distribution 19
2.2.6 Dissolution Test 19
2.3 Analytical Measurements 20
2.3.1 Optical Microscopy (OM) 20
2.3.2 Differential Scanning Calorimetry (DSC) 21
2.3.3 Powder X-ray Diffractometry (PXRD) 21
2.3.4 Ultraviolet and Visible (UV-vis) Spectrophotometry 21
2.4 References 23
Chapter 3 Results and Discussion 24
3.1 1:1 Co-crystal of Acetaminophen-Theophylline Preparation 24
3.1.1 Direct Co-crystal Assembly 26
3.1.2 Re-crystallization 27
3.1.3 Solvent-less Ball-milling 29
3.2 Wet Granulation 37
3.3 Dissolution Test 41
3.4 References 50
Chapter 4 Conclusions and Future Works 53
4.1 Conclusions 53
4.2 Future Works 55
4.3 Reference 56

參考文獻

Chapter 1
Lee, T.; Wang, P. Y. Screening, Manufacturing, Photoluminescence, and Molecular Recognition of Co-crystals: Cytosine With Dicarboxylic Acids. Cryst. Growth Des. 2010, 10(3), 1419–1434.
Desiraju, G. R. Crystal and Co-crystal. CrystEngComm 2003, 5(82), 466–467
Aakery, C. B.; Salmon, D. J. Building Co-crystals With Molecular Sense and Supramolecular Sensibility. CrystEngComm 2005, 7(72), 439–448.
Qiao, N.; Li, M.; Schlindwein, W.; Malek, N.; Davies, A.; Trappitt, G. Pharmaceutical Cocrystals: an Overview. Int. J. Pharm. 2011, 419(1),1 –11.
Karki, S.; Friščić, T.; Fábián, L.; Laity, P. R.; Day, G. M.; Jones, W. Improving Mechanical Properties of Crystalline Solids by Cocrystal Formation: New Compressible Forms of Paracetamol. Adv. Mater. 2009, 21(38-39), 3905–3909.
Schultheiss, N.; Newman, A. Pharmaceutical Cocrystals and Their Physicochemical Properties. Cryst. Growth Des. 2009, 9(6), 2950–2967.
Zhang, J.; Geng, H.; Virk, T. S.; Zhao, Y.; Tan, J.; Di, C. A.; Liu, Y., 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.
Lei, Y. L.; Liao, L. S.; Lee, S. T. Selective Growth of Dual-Color-Emitting Heterogeneous Microdumbbells Composed of Organic Charge-transfer Complexes. J. Am. Chem. Soc. 2013, 135(10), 3744–3747.
Morimoto, M.; Irie, M. A Diarylethene Cocrystal that Converts Light Into Mechanical Work. J. Am. Chem. Soc. 2010, 132(40), 14172–14178.
Karunatilaka, C.; Bučar, D. K.; Ditzler, L. R.; Friščić, T.; Swenson, D. C.; MacGillivray, L. R.; Tivanski, A. V. Softening and Hardening of Macro‐and Nano‐Sized Organic Cocrystals in a Single‐Crystal Transformation. Angew. Chem., Int. Ed. 2011, 50(37), 8642–8646.
Lee, T.; Chen, J. W.; Lee, H. L.; Lin, T. Y.; Tsai, Y. C.; Cheng, S. L.; Chen, L. T. Stabilization and Spheroidization of Ammonium Nitrate: Co-crystallization with Crown Ethers and Spherical Crystallization by Solvent Screening. Chem. Eng. J. 2013, 225(1), 809–817.
Chen, S.; Xi, H.; Henry, R. F.; Marsden, I.; Zhang, G. G. Chiral Co-crystal Solid Solution: Structures, Melting Point Phase Diagram, and Chiral Enrichment of (ibuprofen)2(4,4-dipyridyl). CrystEngComm 2010, 12(5), 1485–1493.
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.
Almarsson, Ö.; Peterson, M. L.; Zaworotko, M. The A to Z of Pharmaceutical Cocrystals: a Decade of Fast-Moving New Science and Patents. Pharm. Pat. Anal. 2012, 1(3), 313–327.
Khan, M.; Enkelmann, V.; Brunklaus, G. Crystal Engineering of Pharmaceutical Co-crystals: Application of Methyl Paraben as Molecular Hook. J. Am. Chem. Soc. 2010, 132(14), 5254–5263.
Jones, W.; Motherwell, W. S.; Trask, A. V. Pharmaceutical Cocrystals: an Emerging Approach to Physical Property Enhancement. MRS Bull. 2006, 31(11), 875–879.
Babu, N. J.; Nangia, A. Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals. Cryst. Growth Des. 2011, 11(7), 2662–2679.
Lee, T.; Chen, H. R.; Lin, H. Y.; Lee, H. L. Continuous Co-crystallization as a Separation Technology: the Study of 1: 2 Co-crystals of Phenazine–Vanillin. Cryst. Growth Des. 2012, 12(12), 5897–5907.
Billot, P.; Hosek, P.; Perrin, M. A. Efficient Purification of an Active Pharmaceutical Ingredient via Cocrystallization: From Thermodynamics to Scale-up. Org. Process Res. Dev. 2013, 17(3), 505–511.
Urbanus, J.; Roelands, C. M.; Verdoes, D.; Jansens, P. J.; ter Horst, J. H. Co-crystallization as a Separation Technology: Controlling Product Concentrations by Co-crystals. Cryst. Growth Des. 2010, 10(3), 1171–1179.
Kim, S.; Li, Z.; Tseng, Y. C.; Nar, H.; Spinelli, E.; Varsolona, R.; Yee, N. Development and Characterization of a Cocrystal as a Viable Solid Form for an Active Pharmaceutical Ingredient. Org. Process Res. Dev. 2013, 17(3), 540–548.
Sekhon, B. S. Drug-drug Co-crystals. J. Pharm. Sci. 2012, 20(1), 45-46.
Leung, D. H.; Lohani, S.; Ball, R. G.; Canfield, N.; Wang, Y.; Rhodes, T.; Bak, A. Two Novel Pharmaceutical Cocrystals of a Development Compound–screening, Scale-up, and Characterization. Cryst. Growth Des. 2012, 12(3), 1254–1262.
Lee, H. L.; Lee, T. Direct Co-crystal Assembly From Synthesis to Co-crystallization. CrystEngComm 2015, 17(47), 9002-9006.
Lin, H. L.; Zhang, G. C.; Hsu, P. C.; Lin, S. Y. A Portable Fiber-Optic Raman Analyzer for Fast Real-Time Screening and Identifying Cocrystal Formation of Drug-Coformer via Grinding Process. Microchem. J. 2013, 110, 15-20.
Lin, S. Y.; Lin, H. L.; Chi, Y. T.; Huang, Y. T.; Kao, C. Y.; Hsieh, W. H. Thermoanalytical and Fourier Transform Infrared Spectral Curve-Fitting Techniques Used to Investigate the Amorphous Indomethacin Formation and Its Physical Stability in Indomethacin-Soluplus® Solid Dispersions. Int. J. Pharm. 2015, 496(2), 457-465.
Zhang, G. C.; Lin, H. L.; Lin, S. Y. Thermal Analysis and FTIR Spectral Curve-Fitting Investigation of Formation Mechanism and Stability of Indomethacin-Saccharin Cocrystals via Solid-State Grinding Process. J. Pharm. Biomed. Anal. 2012, 66, 162-169.
Trask, A. V.; Jones, W. Crystal Engineering of Organic Cocrystals by The Solid-State Grinding Approach. Org. Solid State React. 2005, 254, 41-70.
Karki, S.; Friščić, T.; Jones, W. Control and Interconversion of Cocrystal Stoichiometry in Grinding: Stepwise Mechanism for The Formation of a Hydrogen-Bonded Cocrystal. CrystEngComm 2009, 11(3), 470-481.
Friščić, T.; Jones, W. Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding. Cryst. Growth Des. 2009, 9(3), 1621-1637.
Aghababian, R. (Ed.). Essentials of emergency medicine. Jones & Bartlett Publishers. 2010.
Behring, C. S. L. WHO Model List of Essential Medicines. 19th List. (April 2015) (Amended November 2015)
Griffiths, R. R.; Juliano, L. M.; Chausmer, A. L. Caffeine pharmacology and clinical effects. ASAM, 2003, 3, 193-224.
Karki, S.; Friščić, T.; Fábián, L.; Laity, P. R.; Day, G. M.; Jones, W. Improving Mechanical Properties of Crystalline Solids by Cocrystal Formation: New Compressible Forms of Paracetamol. Adv. Mater. 2009, 21(38‐39), 3905-3909.
Braga, D.; Grepioni, F.; Maini, L.; Mazzeo, P. P.; Rubini, K. Solvent-free Preparation of Co-crystals of Phenazine and Acridine with Vanillin. Thermochim. Acta. 2010, 507–508,1 –8.
Takata, N.; Shiraki, K.; Takano, R.; Hayashi, Y.; Terada, K. Cocrystal Screening of Stanolone and Mestanolone Using Slurry Crystallization. Cryst. Growth Des. 2008, 8(8), 3032–3037.
Croker, D. M.; Rasmuson, Å. C. Isothermal Suspension Conversion as a Route to Cocrystal Production: One-pot Scalable Synthesis. Org. Process Res. Dev. 2014, 18(8), 941–946.
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.
Yu, Z. Q.; Chow, P. S.; Tan, R. B. Operating Regions in Cooling Cocrystallization of Caffeine and Glutaric Acid in Acetonitrile. Cryst. Growth Des. 2010, 10(5), 2382–2387.
Padrela, L.; Rodrigues, M. A.; Velaga, S. P.; Fernandes, A. C.; Matos, H. A.; de Azevedo, E. G. Screening for Pharmaceutical Cocrystals Using the Supercritical Fluid Enhanced Atomization Process. J. Supercrit. Fluids 2010, 53(1), 156–164.
Herrmann, M.; Förter‐Barth, U.; Kröber, H.; Kempa, P. B.; Juez‐Lorenzo, M. D. M.; Doyle, S. Co‐Crystallization and Characterization of Pharmaceutical Ingredients. Part. Part. Syst. Charact. 2009, 26(3), 151–156.
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.
Lee, H. L.; Lin, H. Y.; Lee, T. Large-Scale Crystallization of a Pure Metastable Polymorph by Reaction Coupling. Org. Process Res. Dev. 2014, 18(4), 539-545.
Lee, H. L.; Lee, T. Direct Co-crystal Assembly From Synthesis to Co-crystallization. CrystEngComm 2015, 17(47), 9002-9006.
Braga, D.; Maini, L.; Grepioni, F. Mechanochemical Preparation of Co-crystals. Chem. Soc. Rev. 2013, 42(18), 7638-7648.
Friščić, T.; Jones, W. Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding. Cryst. Growth Des. 2009, 9(3), 1621-1637.
Anastas, P.; Eghbali, N. Green Chemistry: Principles and Practice. Chem. Soc. Rev. 2010, 39(1), 301-312.
Rehder, S.; Christensen, N. P. A.; Rantanen, J.; Rades, T.; Leopold, C. S. High-Shear Granulation as a Manufacturing Method for Cocrystal Granules. Eur J Pharm Biopharm. 2013, 85(3), 1019-1030.
Sládková, V.; Dammer, O.; Sedmak, G.; Skořepová, E.; Kratochvíl, B. Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: in situ Preparation During Formulation. Crystals. 2017, 7(1), 13-29.
Chapter, G. 2040 Disintegration and Dissolution of Dietary Supplements, United States Pharmacopeia 34, National Formulary 29, Rockville, Md., USA, The United States Pharmacopeial Convention. 2011.

Chapter 2
W. Sorasuchart, J. Wardrop, J. W. Ayres, Drug Release from Spray Layered and Coated Drug-Containing Beads: Effects of pH and Comparison of Different Dissolution Methods. Drug Dev. Ind. Pharm. 1999, 25(10), 1093-1098.
S. A. Altaf, S. W. Hoag, J. W. Ayres, Bead Compacts. II. Evaluation of Rapidly Disintegrating Nonsegregating Compressed Bead Formulations. Drug Dev. Ind. Pharm. 1999, 25(5), 635-642.
T. X. Viegas, R. U. Curatella, L. L. Van Winkle, and G. Brinker, Measurement of Intrinsic Drug Dissolution Rates Using Two Types of Apparatus. Pharm. Tech. 2001, 25(6), 44-53.

Chapter 3
Karki, S.; Friščić, T.; Fábián, L.; Laity, P. R.; Day, G. M.; Jones, W. Improving Mechanical Properties of Crystalline Solids by Cocrystal Formation: New Compressible Forms of Paracetamol. Adv. Mater. 2009, 21(38‐39), 3905-3909.
Lee, H. L.; Lin, H. Y.; Lee, T. Large-Scale Crystallization of a Pure Metastable Polymorph by Reaction Coupling. Org. Process Res. Dev. 2014, 18(4), 539-545.
Lee, H. L.; Lee, T. Direct Co-crystal Assembly From Synthesis to Co-crystallization. Cryst Eng Comm. 2015, 17(47), 9002-9006.
Braga, D.; Maini, L.; Grepioni, F. Mechanochemical Preparation of Co-crystals. Chem. Soc. Rev. 2013, 42(18), 7638-7648.
Friščić, T.; Jones, W. Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding. Cryst. Growth Des. 2009, 9(3), 1621-1637.
Anastas, P.; Eghbali, N. Green Chemistry: Principles and Practice. Chem. Soc. Rev. 2010, 39(1), 301-312.
Halasz, I.; Puškarić, A.; Kimber, S. A.; Beldon, P. J.; Belenguer, A. M.; Adams, F.; Štrukil, V. Real‐Time In Situ Powder X‐Ray Diffraction Monitoring of Mechanochemical Synthesis of Pharmaceutical Cocrystals. Angew. Chem. Int. Ed. 2013, 52(44), 11538-11541.
Karki, S.; Friščić, T.; Jones, W. Control and Interconversion of Cocrystal Stoichiometry in Grinding: Stepwise Mechanism for the Formation of a Hydrogen-Bonded Cocrystal. Cryst Eng Comm. 2009, 11(3), 470-481.
Tumanov, I. A.; Achkasov, A. F.; Boldyreva, E. V.; Boldyrev, V. V. Following The Products of Mechanochemical Synthesis Step by Step. Cryst Eng Comm, 2001, 13(7), 2213-2216.
Halasz, I. Single-Crystal-To-Single-Crystal Reactivity: Gray, Rather Than Black Or White. Cryst. Growth Des. 2010, 10(7), 2817-2823.
Cinčić, D.; Friščić, T.; Jones, W. A Stepwise Mechanism for The Mechanochemical Synthesis of Halogen-Bonded Cocrystal Architectures. J. Am. Chem. Soc. 2008, 130(24), 7524-7525.
Nguyen, K. L.; Friščić, T.; Day, G. M.; Gladden, L. F.; Jones, W. Terahertz Time-Domain Spectroscopy and the Quantitative Monitoring of Mechanochemical Cocrystal Formation. Nature Mater. 2007, 6(3), 206-209.
Friščić, T.; Jones, W. Recent Advances in Understanding The Mechanism of Cocrystal Formation via Grinding. Cryst. Growth Des. 2009, 9(3), 1621-1637.
Drits, V.; Srodon, J.; Eberl, D. D. XRD Measurement of Mean Crystallite Thickness of Illite and Illite/Smectite: Reappraisal of the Kubler Index and the Scherrer Equation. Clays Clay Miner. 1997, 45(3), 461-475.
Cleary, P. W. Predicting charge motion, power draw, segregation and wear in ball mills using discrete element methods. Miner. Eng. 1998, 11(11), 1061-1080.
Schmidt, R.; Scholze, H. M.; Stolle, A. Temperature progression in a mixer ball mill. Int. J. Ind. Chem. 2016, 7(2), 181-186.
Lee, H. L.; Lee, T. Direct Co-crystal Assembly From Synthesis to Co-crystallization. Cryst Eng Comm. 2015, 17(47), 9002-9006.
Rehder, S.; Christensen, N. P. A.; Rantanen, J.; Rades, T.; Leopold, C. S. High-Shear Granulation As A Manufacturing Method For Cocrystal Granules. Eur J Pharm Biopharm. 2013, 85(3), 1019-1030.
Sládková, V.; Dammer, O.; Sedmak, G.; Skořepová, E.; Kratochvíl, B. Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation. Crystals. 2017, 7(1), 13.
Lee, T.; Hsu, F. B. 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.

Chapter 4
Friščić, T.; Jones, W. Recent Advances in Understanding The Mechanism of Cocrystal Formation via Grinding. Cryst. Growth Des. 2009, 9(3), 1621-1637.
Tumanov, I. A.; Achkasov, A. F.; Boldyreva, E. V.; Boldyrev, V. V. Following The Products of Mechanochemical Synthesis Step by Step. CrystEngComm 2001, 13(7), 2213-2216.
Halasz, I. Single-Crystal-To-Single-Crystal Reactivity: Gray, Rather Than Black Or White. Cryst. Growth Des. 2010, 10(7), 2817-2823.
Lee, H. L.; Lee, T. Direct Co-crystal Assembly from Synthesis to Co-crystallization.
CrystEngComm 2015, 17(47), 9002-9006.
Rehder, S.; Christensen, N. P. A.; Rantanen, J.; Rades, T.; Leopold, C. S. High-Shear Granulation as a Manufacturing Method for Cocrystal Granules. Eur. J. Pharm. Biopharm. 2013, 85(3), 1019-1030.
Sládková, V.; Dammer, O.; Sedmak, G.; Skořepová, E.; Kratochvíl, B. Ivabradine Hydrochloride (S)-Mandelic Acid Co-Crystal: In Situ Preparation during Formulation. Crystals. 2017, 7(1), 13-29.
Górniak, A.; Wojakowska, A.; Karolewicz, B.; Pluta, J. Phase Diagram and Dissolution Studies of The Fenofibrate–Acetylsalicylic Acid System. J. Therm. Anal. Calorim. 2010, 104(3), 1195-1200.

指導教授

李度(Tu Lee)

審核日期

2017-7-28

推文