| 摘要(英) |
More than 65% of new drug candidates in pharmaceutical industry are poorly aqueous soluble drug. Co-crystallization technique can be used to overcome this problem through enhancing the high-end product purification and bioavailability of the drug by combining the API (Active Pharmaceutical Ingredient) with the co-former agent. In this work, co-crystallization of benzoic acid as the API with sodium benzoate as the co-former in co-solvent of 4:1 v/v of ethanol-water was generated by reaction crystallization method. A clear saturated solution was prepared by diluting Solution A containing 17.22 g (0.141 mol) of benzoic acid (HBz) in 50 mL of 4:1 v/v ethanol – water co-solvent and Solution B containing 1.89 g (0.047 mol) of sodium hydroxide (NaOH) in 6 mL of 2:1 v/v ethanol – water co-solvent. The solution then was cooled from room temperature to 16oC until the crystals were generated and the solution became turbid, indicating that the system had reached the end of the induction time, τ, of crystallization which can be used to determine some fundamental kinetic and thermodynamic parameters of nucleation and crystal growth, such as: the interfacial energy, γ, the Gibbs energetic barrier, ΔGcr, the nucleation rate, J, the critical size of stable nuclei, rc, and the relative growth rate, RG. All of these parameters were evaluated with different initial supersaturation ratio of the system, S0, which were: 1.66, 1.54, 1.48, and 1.43. To study the effect of templating in co-crystal system, about 1.5 wt % template of: sodium benzoate, 2:1 co-crystal of benzoic acid-sodium benzoate, and 1:1 co-crystal of benzoic acid-sodium benzoate were
iii
introduced for each system with different S0. In general, the induction times for all systems ranged from 3 to 40 minutes, where the higher S0 value gave the faster τ value. Moreover, introducing a template in the system gave a faster induction time, τ. ΔGcr and rc decreased, while J and RG increased on a faster induction time, indicating that co-crystallization thermodynamic and kinetic were directly related to the initial concentration of the drug. The final product of the solid crystals for each system was verified as 2:1 co-crystal of benzoic acid – sodium benzoate by PXRD, FTIR, DSC, and TGA. Finally, these results showed that co-crystallization of API, benzoic acid, with its co-former, sodium benzoate, was feasible, both kinetically and thermodynamically. |
| 參考文獻 |
1 Patel, V. R.; Agrawal, Y. K. Nanosuspension: An Approach to Enhance Solubility of Drugs. J. Adv. Pharm. Technol. Res. 2011, 2 (2), 81–87.
2 Sikarra, D.; Shukla, V.; Kharia, A.A.; Chatterjee, D.P. Techniques for Solubility Enhancement of Poorly Soluble Drugs: An Overview. J. Med. Pharm. Sci. 2012, 1, 1-22. 3 Savjani, K. T.; Gajjar, A. K.; Savjani, J. K. Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm. 2012, 2012, 1-10.
4 Prohens, R.; Puigjaner, C. Crystal Engineering Studies: Polymorphs and Co-Crystals, 1st ed.; Centres Científics i Tecnològics. Universitat de Barcelona: Barcelona, BCN, 2012; pp. 3-4. 5 Yadav, A.V.; Shete, A.S.; Dabke, A.P.; Kulkarni, P.V.; Sakhare, S.S. Co-Crystals: A Novel Approach to Modify Physicochemical Properties of Active Pharmaceutical Ingredients. Indian J. Pharm. Sci. 2009, 71 (4), 359-370.
6 Kotak,U.; Prajapati,V.; Solanki, H.; Jani, G.; Jha, P. Co-Crystallization Technique Its Rationale and Recent Progress. J. Pharm. Pharm. Sci. 2015, 4 (04), 1484-1508.
7 Sheikh, A.Y.; Rahim, S.A.; Hammond, R.B.; Roberts, K.J. Scalable Solution Co-Crystallization: Case of Carbamazepine-Nicotinamide I. CrystEngComm 2008, 11 (3), 501-509. 8 Benzoic Acid and Salyclic Acid (topical). https://www.drugs.com/mtm/benzoic-acid-and-salicylic-acid-topical.html (accessed June 5, 2017)
9 Remington, J. P. The Science and Practice of Pharmacy, 2nd ed.; Lippincott Williams &
19
Wilkins: Maryland, Md., 2006; pp: 748. 10 Häberle, J.; Boddaert, N.; Burlina, A.; Chakrapani, A.; Dixon, M.; Huemer, M.; Karall, D.; Martinelli, D.; Crespo, P.; Santer, R.; Servais, A.; Valayannopoulos, V.; Lindner, M.; Rubio, V.; Dionisi-Vici, C. Suggested Guidelines for The Diagnosis and Management of Urea Cycle Disorders. Orphanet J. Rare Dis. 2012, 7 (32), 1-30.
11 World Health Organization. Benzoic Acid and Sodium Benzoate: Concise International Chemical Assessment Document No. 26; Geneva, GA, 2000.
12 Sim, G.A.; Robertson, J.M.; Goodwin, T.H. The Crystal and Molecular Structure of Benzoic Acid. Acta Crystallogr. 1955, 8 (3), 157-164.
13 Martin, T.; Gorelik, T.E..; Greim, D.; Butterhof, C.; Kolb, U.; Senker, J.; Breu, J. Microphase Separation Upon Crystallization of Small Amphiphilic Molecules: ‘Low’ Temperature Form II of Sodium Benzoate (E 211). CrystEngComm 2016, 31 (18), 5779–5966.
14 Deun, R.K.; Ramaekers, J.; Nockemann, P.; Hecke, K.V.; Meervelt, L.V.; Binnemans, K. Alkali Metal Salts of Aromatic Carboxylic Acids: Liquid Crystals without Flexible Chains, J. Inorg. Chem. 2005, 2005 (3), 563-571.
15 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). Z. Anorg. Allg. Chem. 2013, 639 (15), 2816–282.
16 Svoboda, S.; MacFhionnghaile, P.; McGinty, J, Connor, L.E.; Oswald, I. D.H.; Sefcik, J.
20
Continous Co-crystallization of Benzoic Acid and Isonicotinamide by Mixing-Induced Supersaturation: Exploring Oppurtunities Between Reactive and Antisolvent Crystallization Concepts. Cryst. Growth Des. 2017, 17 (4), 1902-1909.
17 Skovgaard, S.; Bond, A.D. Co-crystallisation of Benzoic Acid Derivatives with N-Containing Bases in Solution and by Mechanical Grinding: Stoichiometric Variants, Polymorphism and Twinning. CrystEngComm 2009, 11 (3), 444–453.
18 Butterhof,C.; Milius,W.; Breu, J. Influence of Cation Size on the Co-crystallisation of Benzoic Acid with Different Benzoates. Z. Anorg. Allg. Chem. 2013, 639 (2), 308-311.
19 Butterhof, C.; Barwinkel, K.; Senker, J.; Breu, J. Polymorphism in Co-Crystals: A Metastable Form of the Ionic Co-Crystal 2HBz.1NaBz Crystallized by Flash Evaporation. CrystEngComm 2012, 14 (20), 6744-6749.
20 Butterhoff, C.; Milius, W.; Breu, J. Co-Crystallization of Benzoic Acid with Sodium Benzoate: The Significance of Stoichiometry. CrystEngComm 2012, 14 (11), 3945 – 3950.
21 Lee, H.L.; Lee, T. Direct Co-crystal Assembly from Synthyesis to Co-crystallization. CrystEngComm 2015, 47 (17), 8967-9244.
22 Davey, R.J.; Garside, J. Phase Equilibria and Crystallization Techniques in from Molecules to Crystallizers, 1st ed.; Oxford University Press Inc.: Oxford, OFE, 2000; pp: 26.
23 Urbanus, J.; Roelands, C.P.M.; Horst, J.H.; Verdoes, D. Jansens, P.J. Screening for Templates that Promote Crystallization. Food Bioprod. Process 2008, 86 (2), 116–121.
24 Agnew, L. R.; McGlone, T.; Wheatcroft, H. P.; Robertson, A.; Parsons, A. R.; Wilson, C. C. Continuous Crystallization of Paracetamol (Acetaminophen) Form II: Selective Access to a Metastable Solid Form. Cryst. Growth Des. 2017, 17 (5), 2418–2427.
25 Agnew, L.R.; Cruickshank, D.L.; McGlone, T; Wilson, C.C. Controlled Production of the Elusive Metastable Form II of Acetaminophen (Paracetamol): A Fully Scalable Templating Approach in A Cooling Environment. Chem. Commun. 2016, 52 (46), 7368-7371.
26 Hornedo, N.R.; Nehm, S. J.; Seefeldt, K. F.; Torres, Y. P.; Falkiewicz, C. J. Reaction Crystallization of Pharmaceutical Molecular Complexes. Mol. Pharm. 2006, 3 (3), 362–367. 27 Pharmaceutical “Quality by Design” (QbD): An Introduction, Process Development and Applications.http://learnaboutgmp.com/pharmaceutical-quality-by-design-qbd-an introduction-process-development-and-applications. (accessed July 4, 2017)
28 Lee, T.; Chen, Y. H; Wang, Y. W. Effect of Homochiral Molecules of (S)-(+)-Ibuprofen and (S)-(-)-Sodium Ibuprofen Dihydrate on the Crystallization Kinetics of Racemic (R,S)-(±)-Sodium Ibuprofen Dihydrate. Cryst. Growth Des. 2007, 8 (2), 415-426.
29 Quon, J, L.; Chadwick, K.; Wood, G.P.F.; Sheu, I.; Brettmann, B.K.; Myerson, A.S.; Trout, B. L. Templated Nucleation of Acetaminophen on Spherical Excipient Agglomerates. Langmuir 2013, 29 (10), 3292−3300. 30 Kuldipkumar, A.; Kwon, G. S.; Zhang, G. G. Z. Determining the Growth Mechanism of
22
Tolazamide by Induction Time Measurement. Cryst. Growth Des. 2007, 7 (2), 234–242.
31 Zhou,L.; Wang, Z.; Zhang, M.; Guo, M.; Xu, S.; Yin, Q. Determination of Metastable Zone and Induction Time of Analgin for Cooling Crystallization. Chin. J. Chem. Eng. 2017, 25 (3) 313–318.
32 Sako, K.; Furukawa, Y.; Nakajima, K. Advances in Crystal Growth Research, 1st ed.; Elsevier Science B.V.: Netherland, NL, 2001; pp: 406-407.
33 Mullin, J.W. Crystallization, 4th ed.; Butterworth-Heinemann: Oxford, OFE, 2001; pp: 181-187. |
[Endnote RIS 格式]
[相關文章]
[文章引用]
[完整記錄]
[館藏目錄]
[檢視]
plurk
funp
live
udn
HD
myshare
netvibes
friend
youpush
delicious
baidu
Google bookmarks
del.icio.us
hemidemi
facebook
twitter
google
reddit