Solvent-free Methods for Co-crystal Synthesis: A Review

Author(s): Saroj Kumar*, Om Prakash, Amresh Gupta, Satyawan Singh.

Journal Name: Current Organic Synthesis

Volume 16 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Pharmaceutical co-crystals are the homogeneous crystalline substances composed of two or more substances bound together in the same crystal lattice via noncovalent interactions like hydrogenbonding, electrostatic interaction and Vander Waals interactions. Currently, co-crystals provide excellent opportunities to the formulation scientists in developing new pharmaceutical products by improving the pharmaceutically significant properties like solubility, dissolution rate, bioavailability, stability, and some other derived properties. Due to their ability to improve pharmacokinetic performance and their important intellectual property status, co-crystals are likely to have a very significant role in future drug development. Thus, formulation scientists have their focus on the development aspects of a co-crystallization process that include a rational selection of co-former, the discovery of novel synthetic procedures and new characterization techniques, and large scale production of these novel materials.

Objective: The objective of this article is to present an extensive review of solvent-free methods for co-crystal synthesis, mainly focusing on the principle mechanisms, advantages, and drawbacks of each method.

Conclusion: From the review of the topic, it is clear that the solvent-free methods can offer numerous advantages over solvent-based methods in the design and the production of co-crystals of pharmaceutical use and these methodologies can also pave the path to advancing the field of co-crystal synthesis. Some of the advantages accompanied with solvent-free methods are the use of no or very less amount of solvent(s), exceptional purity and quality of produced co-crystal, large scale production and the short reaction times in few cases.

Keywords: Co-crystals, mechanochemical method, hot melt extrusion, spray congealing, solid state shear milling, microwave-assisted grinding.

[1]
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.
[2]
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.
[3]
Rasenack, N.; Steckel, H.; Müller, B.W. Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process. J. Pharm. Sci., 2003, 92(1), 35-44.
[4]
Umeda, Y.; Fukami, T.; Furuishi, T.; Suzuki, T.; Tanjoh, K.; Tomono, K. Characterization of multicomponent crystal formed between indomethacin and lidocaine. Drug Dev. Ind. Pharm., 2009, 35(7), 843-851.
[5]
Torchilin, V.P. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J., 2007, 9(2), E128-E147.
[6]
Ervasti, T.; Aaltonen, J.; Ketolainen, J. Theophylline-nicotinamide cocrystal formation in physical mixture during storage. Int. J. Pharm., 2015, 486(1-2), 121-130.
[7]
Rahman, Z.; Samy, R.; Sayeed, V.A.; Khan, M.A. Physicochemical and mechanical properties of carbamazepine cocrystals with saccharin. Pharm. Dev. Technol., 2012, 17(4), 457-465.
[8]
Hiendrawan, S.; Veriansyah, B.; Widjojokusumo, E.; Soewandhi, S.N.; Wikarsa, S.; Tjandrawinata, R.R. Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid. Int. J. Pharm., 2016, 497(1-2), 106-113.
[9]
Suzuki, N.; Kawahata, M.; Yamaguchi, K.; Suzuki, T.; Tomono, K.; Fukami, T. Comparison of the relative stability of pharmaceutical cocrystals consisting of paracetamol and dicarboxylic acids. Drug Dev. Ind. Pharm., 2018, 44(4), 582-589.
[10]
Ullah, M.; Hussain, I.; Sun, C.C. The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance. Drug Dev. Ind. Pharm., 2016, 42(6), 969-976.
[11]
Sarkar, A.; Rohani, S. Cocrystals of acyclovir with promising physico-chemical properties. J. Pharm. Sci., 2015, 104(1), 98-105.
[12]
Nechipadappu, S.K.; Tekuri, V.; Trivedi, D.R. Pharmaceutical co-crystal of flufenamic acid: synthesis and characterization of two novel drug-drug co-crystal. J. Pharm. Sci., 2017, 106(5), 1384-1390.
[13]
Bhatt, P.M.; Azim, Y.; Thakur, T.S.; Desiraju, G.R. Co-crystals of the anti-hiv drugs lamivudine and zidovudine. Cryst. Growth Des., 2009, 9(2), 951-957.
[14]
Malamatari, M.; Ross, S.A.; Douroumis, D.; Velaga, S.P. Experimental cocrystal screening and solution based scale-up cocrystallization methods. Adv. Drug Deliv. Rev., 2017, 117, 162-177.
[15]
Healy, A.M.; Worku, Z.A.; Kumar, D.; Madi, A.M. Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals. Adv. Drug Deliv. Rev., 2017, 117, 25-46.
[16]
Cerreia Vioglio, P.; Chierotti, M.R.; Gobetto, R. Pharmaceutical aspects of salt and cocrystal forms of apis and characterization challenges. Adv. Drug Deliv. Rev., 2017, 117, 86-110.
[17]
Savjani, J. Co-crystallization: An approach to improve the performance characteristics of active pharmaceutical ingredients. Asian J. Pharm., 2015, 9(3), 147.
[18]
Izutsu, K.; Koide, T.; Takata, N.; Ikeda, Y.; Ono, M.; Inoue, M.; Fukami, T.; Yonemochi, E. Characterization and quality control of pharmaceutical cocrystals. Chem. Pharm. Bull. (Tokyo), 2016, 64(10), 1421-1430.
[19]
Shan, N.; Zaworotko, M.J. The role of cocrystals in pharmaceutical science. Drug Discov. Today, 2008, 13(9-10), 440-446.
[20]
Thipparaboina, R.; Kumar, D.; Chavan, R.B.; Shastri, N.R. Multidrug co-crystals: towards the development of effective therapeutic hybrids. Drug Discov. Today, 2016, 21(3), 481-490.
[21]
Lorenzo, D.A.; Forrest, S.J.K.; Sparkes, H.A. Crystal engineering: Co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer. Acta Crystallogr. Sect. B Struct. Sci. Cryst. Eng. Mater., 2016, 72(1), 87-95.
[22]
Aakeröy, C.B.; Salmon, D.J. Building co-crystals with molecular sense and supramolecular sensibility. CrystEngComm, 2005, 7(72), 439-448.
[23]
Aakeröy, C.B.; Beatty, A.M.; Helfrich, B.A. A high-yielding supramolecular reaction. J. Am. Chem. Soc., 2002, 124(48), 14425-14432.
[24]
Almarsson, Ö.; Zaworotko, M.J. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chem. Commun., 2004, (17), 1889-1896.
[25]
Childs, S.L.; Zaworotko, M.J. The reemergence of cocrystals: the crystal clear writing is on the wall introduction to virtual special issue on pharmaceutical cocrystals. Cryst. Growth Des., 2009, 9(10), 4208-4211.
[26]
Moradiya, H.G.; Islam, M.T.; Halsey, S.; Maniruzzaman, M.; Chowdhry, B.Z.; Snowden, M.J.; Douroumis, D. Continuous cocrystallisation of carbamazepine and trans-cinnamic acid via melt extrusion processing. CrystEngComm, 2014, 16(17), 3573-3583.
[27]
Eddleston, M.D.; Patel, B.; Day, G.M.; Jones, W. Cocrystallization by freeze-drying: Preparation of novel multicomponent crystal forms. Cryst. Growth Des., 2013, 13(10), 4599-4606.
[28]
Hasa, D.; Schneider, G.; Voinovich, D.; Jones, W. Cocrystal formation through mechanochemistry: From neat and liquid-assisted grinding to polymer-assisted grinding. Angew. Chemie. Int. Ed., 2015, 54(25), 7371-7375.
[29]
Braga, D.; Maini, L.; Grepioni, F. Mechanochemical preparation of co-crystals. Chem. Soc. Rev., 2013, 42(18), 7638-7648.
[30]
Braga, D.; Giaffreda, S.L.; Rubini, K.; Grepioni, F.; Chierotti, M.R.; Gobetto, R. Making crystals from crystals: Three solvent-free routes to the hydrogen bonded co-crystal between 1,1′-di-pyridyl-ferrocene and anthranilic acid. CrystEngComm, 2007, 9(1), 39-45.
[31]
James, S.L.; Adams, C.J.; Bolm, C.; Braga, D.; Collier, P.; Friić, T.; Grepioni, F.; Harris, K.D.M.; Hyett, G.; Jones, W.; Krebs, A.; Mack, J.; Maini, L.; Orpen, A.G.; Parkin, I.P.; Shearouse, W.C.; Steed, J.W.; Waddell, D.C. Mechanochemistry: Opportunities for new and cleaner synthesis. Chem. Soc. Rev., 2012, 41(1), 413-447.
[32]
Dubois, J.; Colaco, M.; Wouters, J. Mechanosynthesis, a method of choice in solid a method of choice in solid state synthesis state synthesis. Chim. Nouv, 2014, (1), 21-30.
[33]
Wieczorek-Ciurowa, K.; Gamrat, K. Some aspects of mechanochemical reactions. Mater. Sci., 2007, 25(1), 219-232.
[34]
Etter, M.C.; Zia-Ebrahimi, M.; Urbañczyk-Lipkowska, Z.; Panunto, T.W. Hydrogen bond directed cocrystallization and molecular recognition pro-perties of diarylureas. J. Am. Chem. Soc., 1990, 112(23), 8415-8426.
[35]
Do, J.L.; Friščić, T. Mechanochemistry: A force of synthesis. ACS Cent. Sci., 2017, 3(1), 13-19.
[36]
Karki, S.; Friščića, 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.
[37]
Chadwick, K.; Davey, R.; Cross, W. How does grinding produce co-crystals? Insights from the case of benzophenone and diphenylamine. CrystEngComm, 2007, 9(9), 732-734.
[38]
Lien Nguyen, K.; Friščić, T.; Day, G.M.; Gladden, L.F.; Jones, W. Terahertz time-domain spectroscopy and the quantitative monitoring of mechano-chemical cocrystal formation. Nat. Mater., 2007, 6(3), 206-209.
[39]
Jayasankar, A.; Somwangthanaroj, A.; Shao, Z.J.; Rodríguez-Hornedo, N. Cocrystal formation during cogrinding and storage is mediated by amorphous phase. Pharm. Res., 2006, 23(10), 2381-2392.
[40]
Rehder, S.; Klukkert, M.; Löbmann, K.A.M.; Strachan, C.J.; Sakmann, A.; Gordon, K.; Rades, T.; Leopold, C.S. Investigation of the formation process of two piracetam cocrystals during grinding. Pharmaceutics, 2011, 3(4), 706-722.
[41]
Kaupp, G. Organic solid-state reactions with 100% yield. Top. Curr. Chem., 2005, 254, 95-183.
[42]
Friščić, T.; Childs, S.L.; Rizvi, S.A.A.; Jones, W. The role of solvent in mechanochemical and sonochemical cocrystal formation: A solubility-based approach for predicting cocrystallisation outcome. CrystEngComm, 2009, 11(3), 418-426.
[43]
Imai, Y.; Tajima, N.; Sato, T.; Kuroda, R. Molecular recognition in solid-state crystallization: Colored chiral adduct formations of 1,1′-bi-2-naphthol derivatives and benzoquinone with a third component. Chirality, 2002, 14(7), 604-609.
[44]
Patil, A.O.; Curtin, D.Y.; Paul, I.C. Interconversion by hydrogen transfer of unsymmetrically substituted quinhydrones in the solid State. Crystal structure of the 1:2 complex of 2,5-dimethylbenzoquinone with hydro-quinone. J. Am. Chem. Soc., 1984, 106(14), 4010-4015.
[45]
Chieng, N.; Hubert, M.; Saville, D.; Rades, T.; Aaltonen, J. Formation kinetics and stability of carbamazepine # nicotinamide cocrystals prepared by mechanical activation formation kinetics and stability of carbamazepinenicotinamide cocrystals prepared by mechanical activation XXXX. Cryst. Growth Des., 2009, 9(form I), 2377-2386.
[46]
Trask, A.V.; Samuel Motherwell, W.D.; Jones, W. Pharmaceutical cocry-stallization: Engineering a remedy for caffeine hydration. Cryst. Growth Des., 2005, 5(3), 1013-1021.
[47]
Heiden, S.; Tröbs, L.; Wenzel, K-J.; Emmerling, F. Mechanochemical synthesis and structural characterisation of a theophylline-benzoic acid cocrystal (1 : 1). CrystEngComm, 2012, 14(16), 5128.
[48]
Friščić, T.; Trask, A.V.; Jones, W.; Motherwell, W.D.S. Screening for inclusion compounds and systematic construction of three-component solids by liquid-assisted grinding. Angew. Chem. Int. Ed., 2006, 45(45), 7546-7550.
[49]
Otsuka, Y.; Ito, A.; Takeuchi, M.; Tanaka, H. Dry mechanochemical synthesis of caffeine/oxalic acid cocrystals and their evaluation by powder X-ray diffraction and chemometrics. J. Pharm. Sci., 2017, 106(12), 3458-3464.
[50]
Basavoju, S.; Boström, D.; Velaga, S.P. Indomethacin-saccharin cocrystal: Design, Synthesis and preliminary pharmaceutical characterization. Pharm. Res., 2008, 25(3), 530-541.
[51]
Trask, A.V.; Shan, N.; Motherwell, W.D.S.; Jones, W.; Feng, S.; Tan, R.B.H.; Carpenter, K.J. Selective polymorph transformation via solvent-drop grinding. Chem. Commun., 2005, (7), 880-882.
[52]
Ross, S.A.; Lamprou, D.A.; Douroumis, D. Engineering and manufacturing of pharmaceutical co-crystals: A review of solvent-free manufacturing technologies. Chem. Commun., 2016, 52(57), 8772-8786.
[53]
Shan, N.; Toda, F.; Jones, W. Mechanochemistry and co-crystal formation: effect of solvent on reaction kinetics. Chem. Commun., 2002, 2(20), 2372-2373.
[54]
Berry, D.J.; Seaton, C.C.; Clegg, W.; Harrington, R.W.; Coles, S.J.; Horton, P.N.; Hursthouse, M.B.; Storey, R.; Jones, W.; Friščić, T.; Blagden, N. Applying hot-stage microscopy to co-crystal screening: A study of nicotinamide with seven active pharmaceutical ingredients. Cryst. Growth Des., 2008, 8(5), 1697-1712.
[55]
Karki, S.; Fabian, L.; Friscic, T.; Jones, W. Powder X-ray diffraction emerging method characterize organic solids. Org. Lett., 2007, 9(16), 3133-3136.
[56]
Madusanka, N.; Mark, D. Crystal engineering polymorphs, hydrates and solvates of a co-crystal of caffeine with anthranilic acid crystal engineering., 2014, 2012, 72-80.
[57]
Weyna, D.R.; Shattock, T.; Vishweshwar, P.; Zaworotko, M.J. Synthesis and structural characterization of cocrystals and pharmaceutical cocrystals: Mechanochemistry vs slow evaporation from solution. Cryst. Growth Des., 2009, 9(2), 1106-1123.
[58]
Trask, A.V.; Motherwell, W.D.S.; Jones, W. Solvent-drop grinding: Green polymorph control of cocrystallisation. Chem. Commun., 2004, (7), 890.
[59]
Trask, A.V.; Van De Streek, J.; Motherwell, W.D.S.; Jones, W. Achieving polymorphic and stoichiometric diversity in cocrystal formation: importance of solid-state grinding, powder x-ray structure determination, and seeding. Cryst. Growth Des., 2005, 5(6), 2233-2241.
[60]
Jones, W.; Eddleston, M.D. Introductory lecture: Mechanochemistry, a versatile synthesis strategy for new materials. Faraday Discuss., 2014, 170, 9-34.
[61]
Jung, S.; Choi, I.; Kim, I. Liquid-assisted grinding to prepare a cocrystal of adefovir dipivoxil thermodynamically less stable than its neat phase. Crystals, 2015, 5(4), 583-591.
[62]
Reichert, W.M.; Holbrey, J.D.; Vigour, K.B.; Morgan, T.D.; Broker, G.A.; Rogers, R.D. Approaches to crystallization from ionic liquids: complex solvents-complex results, or, a strategy for controlled formation of new supramolecular architectures? Chem. Commun., 2006, (46), 4767-4779.
[63]
Rogers, R.D. Cocrystal Formation by Ionic Liquid-Assisted Grinding: Case Study with Cocrystals of Caffeine. CrystEngComm, 2018, 20, 1-5.
[64]
Tan, D.; Loots, L.; Friščić, T. Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs). Chem. Commun., 2016, 52(50), 7760-7781.
[65]
Korde, S.; Pagire, S.; Pan, H.; Seaton, C.; Kelly, A.; Chen, Y.; Wang, Q.; Coates, P.; Paradkar, A. Continuous manufacturing of cocrystals using solid state shear milling technology. Cryst. Growth Des., 2018, 18(4), 2297-2304.
[66]
Liu, X.; Lu, M.; Guo, Z.; Huang, L.; Feng, X.; Wu, C. Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion. Pharm. Res., 2012, 29(3), 806-817.
[67]
Crawford, D.E. Extrusion - Back to the future: Using an established technique to reform automated chemical synthesis. Beilstein J. Org. Chem., 2017, 13, 65-75.
[68]
Paradkar, A.; Dhumal, R.S.; Kelly, A.L.; York, P.; Coates, P.D. Cocrystalization and simultaneous agglomeration using hot melt extrusion. Pharm. Res., 2010, 27(12), 2725-2733.
[69]
Crowley, M.M.; Zhang, F.; Repka, M.A.; Thumma, S.; Upadhye, S.B.; Battu, S.K.; McGinity, J.W.; Martin, C. Pharmaceutical applications of hot-melt extrusion: Part I. Drug Dev. Ind. Pharm., 2007, 33(9), 909-926.
[70]
Douroumis, D. Hot-Melt Extrusion: Pharmaceutical Applications; John Wiley & Sons: UK, 2012.
[71]
Follonier, N.; Doelker, E.; Cole, E.T. Evaluation of hot-melt extrusion as a new technique for the production of polymer-based pellets for sustained release capsules containing high loadings of freely soluble drugs. Drug Development and Industrial Pharmacy., 1994, 20(8), 1323-1339.
[72]
Crowley, M.M.; Fredersdorf, A.; Schroeder, B.; Kucera, S.; Prodduturi, S.; Repka, M.A.; McGinity, J.W. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. Eur. J. Pharm. Sci., 2004, 22(5), 409-418.
[73]
Breitenbach, J. Melt extrusion: From process to drug delivery technology. Eur. J. Pharm. Biopharm., 2002, 54(2), 107-117.
[74]
Nikitine, C.; Rodier, E.; Sauceau, M.; Fages, J. Residence time distribution of a pharmaceutical grade polymer melt in a single screw extrusion process. Chem. Eng. Res. Des., 2009, 87(6), 809-816.
[75]
Moradiya, H.; Islam, M.T.; Woollam, G.R.; Slipper, I.J.; Halsey, S.; Snowden, M.J.; Douroumis, D. Continuous cocrystallization for dissolution rate optimization of a poorly water-soluble drug. Cryst. Growth Des., 2014, 14(1), 189-198.
[76]
Boksa, K.; Otte, A.; Pinal, R. Matrix-Assisted Cocrystallization (MAC) simultaneous production and formulation of pharmaceutical cocrystals by hot-melt extrusion. J. Pharm. Sci., 2014, 103(9), 2904-2910.
[77]
Duarte, Í.; Andrade, R.; Pinto, J.F.; Temtem, M. Green production of cocrystals using a new solvent-free approach by spray congealing. Int. J. Pharm., 2016, 506(1-2), 68-78.
[78]
Douroumis, D.; Ross, S.A.; Nokhodchi, A. Advanced methodologies for cocrystal synthesis. Adv. Drug Deliv. Rev., 2017, 117, 178-195.
[79]
Pagire, S.; Korde, S.; Ambardekar, R.; Deshmukh, S.; Dash, R.C.; Dhumal, R.; Paradkar, A. Microwave assisted synthesis of caffeine/maleic acid co-crystals: the role of the dielectric and physicochemical properties of the solvent. CrystEngComm, 2013, 15(18), 3705-3710.
[80]
Titapiwatanakun, V.; Basit, A.W.; Gaisford, S. A new method for producing pharmaceutical co-crystals: Laser irradiation of powder blends. Cryst. Growth Des., 2016, 16(6), 3307-3312.
[81]
Boterashvili, M.; Lahav, M.; Shankar, S.; Facchetti, A.; Boom, M. E.; Van Der, On-surface solvent-free crystal-to-co-crystal conversion by noncovalent interactions. 2014, 136(34), 11926-11929.
[82]
Am Ende, D.J.; Anderson, S.R.; Salan, J.S. Development and scale-up of cocrystals using resonant acoustic mixing. Org. Process Res. Dev., 2014, 18(2), 331-341.
[83]
Jerry, S.; Anderson, S.R.; Am Ende, D. A method to produce and scale-up cocrystals and salts via resonant acoustic mixing. Eur. Pat. Appl., 2014, 2845852A1.
[84]
Nagapudi, K.; Umanzor, E.Y.; Masui, C. High-throughput screening and scale-up of cocrystals using resonant acoustic mixing. Int. J. Pharm., 2017, 521(1-2), 337-345.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 3
Year: 2019
Page: [385 - 397]
Pages: 13
DOI: 10.2174/1570179416666190329194926
Price: $58

Article Metrics

PDF: 44
HTML: 2

Special-new-year-discount