Pharmaceutical cocrystal and their role in improving solid state properties of active pharmaceutical ingredients

Authors

  • Ameera A Radhi Department of pharmaceutics, College of pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Iman S Jaafar Department of pharmaceutics, College of pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Noor S Jaafar Department of Pharmacognosy and Medicinal Plants, College of Pharmacy, University of Baghdad, Baghdad, Iraq
  • Sarah M Faisal Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq

DOI:

https://doi.org/10.32947/ajps.v23i2.1019

Keywords:

Cocrystal, dissolution rate, solubility

Abstract

Cocrystallization is an emerging approach for improving physico-chemical characteristics of an active pharmaceutical ingredient (API) for instance dissolution rate, solubility, stability in addition to mechanical

properties without affecting their therapeutic activity. It is of great importance when other approaches like salt or polymorph formation do not encounter the estimated targets.

In this review article, an outline of pharmaceutical cocrystals will be presented, with highlighting on factors affecting cocrystallization which include ∆pKa, donors and acceptors hydrogen bonds, molecular recognition point, synthon forming functional groups flexibility, dicarboxylic acid coformers carbon chain length and solvent effect, as well as and the methods for cocrystal preparation. Additionally, cocrystal characterization, dissolution pattern as well as the commercially available products were discussed.

References

- Dakhil I, Mahdi Z. An Overview on the Recent Technologies and Advances in Drug Delivery of Poorly Water-Soluble Drugs.AJPS 2019;19(4 ):180-195. DOI: https://doi.org/10.32947/ajps.v19i4.649

- Najm, A , Ali W. Preparation and in-Vitro Evaluation of Cinnarizine Raft Forming Chewable Tablets .AJPS 2019;19(3):42-53. DOI: https://doi.org/10.32947/ajps.v19i3.623

- Wróblewska A, Śniechowska J, Kaźmierski S, Wielgus E, Bujacz GD, Mlostoń G, et al. Application of 1-Hydroxy-4, 5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals. Pharma-ceutics 2020;12(4):359. DOI: https://doi.org/10.3390/pharmaceutics12040359

- Blagden N, Coles S, Berry D. Pharmaceutical co-crystals–are we there yet? Cryst Eng Comm 2014; 16(26):5753-61. DOI: https://doi.org/10.1039/C4CE00127C

- Grothe E, Meekes H, Vlieg E, Ter Horst J, de Gelder Rd. Solvates, salts, and cocrystals: a proposal for a feasible classification system. Crystal growth & design 2016;16(6):3237-43. DOI: https://doi.org/10.1021/acs.cgd.6b00200

- Elder DP, Holm R, Diego HL. Use of pharmaceutical salts and cocrystals to address the issue of poor solubility. Int J Pharm 2013;453(1):88-100. DOI: https://doi.org/10.1016/j.ijpharm.2012.11.028

- Stahly GP. A survey of cocrystals reported prior to 2000. Crystal Growth & Design 2009;9(10):4212-29. DOI: https://doi.org/10.1021/cg900873t

- Aitipamula S, Banerjee R, Bansal AK, Biradha K, Cheney ML, Choudhury AR, et al. Polymorphs, salts, and cocrystals: what’s in a name? Crystal growth & design 2012;12(5):2147-52. DOI: https://doi.org/10.1021/cg3002948

- Gadade DD, Pekamwar SS. Pharmaceutical cocrystals: regulatory and strategic aspects, design and development. Adv Pharm Bull 2016 ;6(4):479. DOI: https://doi.org/10.15171/apb.2016.062

- Xue N, Jia Y, Li C, He B, Yang C, Wang J. Characterizations and Assays of α-Glucosidase Inhibition Activity on Gallic Acid Cocrystals: Can the Cocrystals be Defined as a New Chemical Entity During Binding with the α-Glucosidase. Molecules 2020; 25(5):1163. DOI: https://doi.org/10.3390/molecules25051163

- Vaghela P, Tank H, Jalpa P. Cocrystals: A novel approach to improve the physicochemical and mechanical properties. Indo Am J Pharm Res 2014;4(10):5055-65.

- Kuminek G, Rodríguez-Hornedo N, Siedler S, Rocha H, Cuffini S, Cardoso S. How cocrystals of weakly basic drugs and acidic coformers might modulate solubility and stability. Chem Commun 2016;52 (34):5832-5. DOI: https://doi.org/10.1039/C6CC00898D

- Cysewski P, Przybyłek M. Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index. Eur J Pharm Sci 2017;107:87-96. DOI: https://doi.org/10.1016/j.ejps.2017.07.004

- Cerreia Vioglio P, Chierotti MR, Gobetto R. Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges. Adv Drug Deliv Rev 2017;117:86-110. DOI: https://doi.org/10.1016/j.addr.2017.07.001

- Sanphui P, Mishra MK, Ramamurty U, Desiraju GR. Tuning mechanical properties of pharmaceutical crystals with multicomponent crystals: voriconazole as a case study. Mol Pharm 2015;12(3):889-97. DOI: https://doi.org/10.1021/mp500719t

- Kavanagh ON, Croker DM, Walker GM, Zaworotko MJ. Pharmaceutical cocrystals: from serendipity to design to application. Drug Discov Today 2019;24(3):796-804. DOI: https://doi.org/10.1016/j.drudis.2018.11.023

- Childs SL, Stahly GP, Park A. The salt− cocrystal continuum: the influence of crystal structure on ionization state. Mol Pharm 2007; 4(3):323-38. DOI: https://doi.org/10.1021/mp0601345

- Berry DJ, Steed JW. Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design. Adv Drug Deliv Rev 2017;117:3-24. DOI: https://doi.org/10.1016/j.addr.2017.03.003

- Shattock TR, Arora KK, Vishweshwar P, Zaworotko MJ. Hierarchy of supramolecular synthons: persistent carboxylic acid· pyridine hydrogen bonds in cocrystals that also contain a hydroxyl moiety. Crystal growth & design 2008;8(12):4533-45. DOI: https://doi.org/10.1021/cg800565a

- da Silva CC, Pepino RdO, de Melo CC, Tenorio JC, Ellena J. Controlled Synthesis of New 5-Fluorocytosine Cocrystals Based on the p K a Rule. Crystal Growth & Design 2014;14 (9):4383-93. DOI: https://doi.org/10.1021/cg500502j

- Rajput L, Banik M, Yarava JR, Joseph S, Pandey MK, Nishiyama Y, et al. Exploring the salt–cocrystal continuum with solid-state NMR using natural-abundance samples: implications for crystal engineering. IUCrJ 2017;4(4):466-75. DOI: https://doi.org/10.1107/S205225251700687X

- Mittapalli S, Mannava MC, Khandavilli UR, Allu S, Nangia A. Soluble salts and cocrystals of clotrimazole. Crystal Growth & Design 2015;15(5):2493-504. DOI: https://doi.org/10.1021/acs.cgd.5b00268

- Aitipamula S, Chow PS, Tan RB. Polymorphism in cocrystals: a review and assessment of its significance. Cryst Eng Comm 2014;16(17):3451-65. DOI: https://doi.org/10.1039/c3ce42008f

- Etter MC. Encoding and decoding hydrogen-bond patterns of organic compounds. Acc Chem Res 1990 ;23(4):120-6. DOI: https://doi.org/10.1021/ar00172a005

- Donohue J. The hydrogen bond in organic crystals. The Journal of Physical Chemistry 1952;56(4):502-10. DOI: https://doi.org/10.1021/j150496a023

- Etter MC. Hydrogen bonds as design elements in organic chemistry. J Phys Chem 1991;95(12):4601-10. DOI: https://doi.org/10.1021/j100165a007

- Desiraju GR. Designer crystals: intermolecular interactions, network structuresand supramolecular synth-ons. Chem Comm 1997(16) :1475-82. DOI: https://doi.org/10.1039/a607149j

- Almarsson Ö, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharma-ceutical co-crystals represent a new path to improved medicines? Chem Comm 2004(17):1889-96. DOI: https://doi.org/10.1039/b402150a

- Corey EJ. General methods for the construction of complex molecules. Pure Appl Chem 1967;14(1):19-38. DOI: https://doi.org/10.1351/pac196714010019

- Bavishi DD, Borkhataria CH. Spring and parachute: How cocrystals enhance solubility. Prog Cryst Growth and Ch 2016;62(3):1-8. DOI: https://doi.org/10.1016/j.pcrysgrow.2016.07.001

- Cherukuvada S, Nangia A. Eutectics as improved pharmaceutical materials: design, properties and character-ization. Chem Comm 2014;50(8):906-23. DOI: https://doi.org/10.1039/C3CC47521B

- Aakeröy CB, Beatty AM, Helfrich BA, Nieuwenhuyzen M. Do polymo-rphic compounds make good cocrys-tallizing agents? A structural case study that demonstrates the importance of synthon flexibility. Crystal growth & design 2003; 3(2):159-65. DOI: https://doi.org/10.1021/cg025593z

- Shevchenko A, Miroshnyk I, Pietilä L-O, Haarala J, Salmia J, Sinervo K, et al. Diversity in itraconazole cocrystals with aliphatic dicarboxylic acids of varying chain length. Crystal growth & design 2013;13(11):4877-84. DOI: https://doi.org/10.1021/cg401061t

- Lee KS, Kim KJ, Ulrich J. Formation of Salicylic Acid/4, 4′‐Dipyridyl Cocrystals Based on the Ternary Phase Diagram. Chem Eng Technol 2015;38(6):1073-80. DOI: https://doi.org/10.1002/ceat.201400738

- Robertson CC, Wright JS, Carrington EJ, Perutz RN, Hunter CA, Brammer L. Hydrogen bonding vs. halogen bonding: the solvent decides. Chem Sci 2017;8(8):5392-8. DOI: https://doi.org/10.1039/C7SC01801K

- Douroumis D, Ross SA, Nokhodchi A. Advanced methodologies for cocrystal synthesis. Adv Drug Deliv Rev 2017;117:178-95. DOI: https://doi.org/10.1016/j.addr.2017.07.008

- Moradiya H, Islam MT, Woollam GR, Slipper IJ, Halsey S, Snowden MJ, et al. Continuous cocrystallization for dissolution rate optimization of a poorly water-soluble drug. Crystal Growth & Design 2013;14(1):189-98. DOI: https://doi.org/10.1021/cg401375a

- Baláž P, Achimovičová M, Baláž M, Billik P, Cherkezova-Zheleva Z, Criado JM, et al. Hallmarks of mechanochemistry: from nano-particles to technology. Chem Soc Rev 2013;42(18):7571-637. DOI: https://doi.org/10.1039/c3cs35468g

- Thayyil AR, Juturu T, Nayak S, Kamath S. Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Appl-ications. Adv Pharm Bull 2020 ;10(2):203. DOI: https://doi.org/10.34172/apb.2020.024

- Trask AV, Motherwell WS, Jones W. Pharmaceutical cocrystallization: eng-ineering a remedy for caffeine hydration. Crystal Growth & Design 2005;5(3):1013-21. DOI: https://doi.org/10.1021/cg0496540

- Heiden S, Tröbs L, Wenzel K-J, Emmerling F. Mechanochemical synthesis and structural characte-risation of a theophylline-benzoic acid cocrystal (1:1). Cryst Eng Comm 2012;14(16):5128-9. DOI: https://doi.org/10.1039/c2ce25236h

- Shan N, Toda F, Jones W. Mechanochemistry and co-crystal formation:effect of solvent on reaction kinetics. Chem Comm 2002 (20) :2372-3. DOI: https://doi.org/10.1039/b207369m

- Friščić T, Childs SL, Rizvi SA, Jones W. The role of solvent in mechanochemical and sonochemical cocrystal formation: a solubility-based approach for predicting cocrystall-isation outcome. Cryst Eng Comm 2009;11(3):418-26. DOI: https://doi.org/10.1039/B815174A

- Kumar Bandaru R, Rout SR, Kenguva G, Gorain B, Alhakamy NA, Kesharwani P and Dandela R Recent Advances in Pharmaceutical Cocrys-tals: From Bench to Market. Front. Pharmacol 2021; 12:780582. DOI: https://doi.org/10.3389/fphar.2021.780582

- Madusanka N, Eddleston MD, Arhangelskis M, Jones W. Polymorphs, hydrates and solvates of a co-crystal of caffeine with anthranilic acid. Acta Crystallog B 2014;70(1):72-80. DOI: https://doi.org/10.1107/S2052520613033167

- Karimi-Jafari M, Padrela L, Walker GM, Croker DM. Creating Cocrystals: A Review of Pharmaceutical Cocrystal Preparation Routes and Applications. Crystal Growth & Design 2018;18(10):6370-87. DOI: https://doi.org/10.1021/acs.cgd.8b00933

- He G, Jacob C, Guo L, Chow PS, Tan RB. Screening for cocrystallization tendency: the role of intermolecular interactions. J Phys Chem B 2008 ;112(32):9890-5. DOI: https://doi.org/10.1021/jp803019m

- Rodrigues M, Baptista B, Lopes JA, Sarraguca MC. Pharmaceutical cocr-ystallization techniques. Advances and challenges. Int J Pharm 2018 ;547(1-2):404-20. DOI: https://doi.org/10.1016/j.ijpharm.2018.06.024

- Alhalaweh A, Velaga SP. Formation of cocrystals from stoichiometric solutions of incongruently saturating systems by spray drying. Crystal Growth & Design 2010;10(8):3302-5. DOI: https://doi.org/10.1021/cg100451q

- Alhalaweh A, Kaialy W, Buckton G, Gill H, Nokhodchi A, Velaga SP. Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization perform-ance. AAPS Pharm Sci Tech 2013 ;14(1):265-76. DOI: https://doi.org/10.1208/s12249-012-9883-3

- Wang I-C, Lee M-J, Sim S-J, Kim W-S, Chun N-H, Choi GJ. Anti-solvent co-crystallization of carbamazepine and saccharin. Int J Pharm 2013; 450(1-2):311-22. DOI: https://doi.org/10.1016/j.ijpharm.2013.04.012

- Lange L, Heisel S, Sadowski G. Predicting the solubility of pharma-ceutical cocrystals in solvent/anti-solvent mixtures. Molecules 2016; 21(5):593. DOI: https://doi.org/10.3390/molecules21050593

- Chun N-H, Wang I-C, Lee M-J, Jung Y-T, Lee S, Kim W-S, et al. Characteristics of indomethacin–saccharin (IMC–SAC) co-crystals prepared by an anti-solvent crysta-llization process. Eur J Pharm Biopharm 2013;85(3):854-61. DOI: https://doi.org/10.1016/j.ejpb.2013.02.007

- Eddleston MD, Patel B, Day GM, Jones W. Cocrystallization by freeze-drying: preparation of novel multi-component crystal forms. Crystal Growth & Design 2013;13(10):4599-606. DOI: https://doi.org/10.1021/cg401179s

- Iveson SM, Litster JD, Hapgood K, Ennis BJ. Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review. Powder Technol 2001;117(1-2):3-39. DOI: https://doi.org/10.1016/S0032-5910(01)00313-8

- Rehder S, Christensen NPA, Rantanen J, Rades T, Leopold CS. High-shear granulation as a manufacturing method for cocrystal granules. Eur J Pharm Biopharm 2013;85(3):1019-30. DOI: https://doi.org/10.1016/j.ejpb.2013.04.022

- Müllers KC, Paisana M, Wahl MA. Simultaneous formation and micro-nization of pharmaceutical cocrystals by rapid expansion of supercritical solutions (RESS). Pharm Res 2015; 32(2):702-13. DOI: https://doi.org/10.1007/s11095-014-1498-9

- Pando C, Cabanas A, Cuadra IA. Preparation of pharmaceutical co-crystals through sustainable processes using supercritical carbon dioxide: a review. RSC Advances 2016;6(75) :71134-50. DOI: https://doi.org/10.1039/C6RA10917A

- Shikhar A, Bommana M. M., Simer-deep Singh Gupta SS, Squillante E. Development of Carbamazepine–Nicotinamide co-crystals complexed with γ-cyclodextrin using supercritical fluid process, The Journal of Super-critical Fluids. 2011; 55(3):1070-1078 52. Courtney A. Ober, DOI: https://doi.org/10.1016/j.supflu.2010.09.009

- Ram B. Gupta, Formation of Itraconazole– Succinic Acid Cocry-stals by Gas Antisolvent Cocrysta-llization, AAPS Pharm Sci Tech. 2012; 13(4):1396–1406. DOI: https://doi.org/10.1208/s12249-012-9866-4

- Sanphui P, Bolla G, Nangia A, Chernyshev V. Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt. IUCrJ 2014;1 (2):136-50. DOI: https://doi.org/10.1107/S2052252514004229

- Chadha K, Karan M, Bhalla Y, Chadha R, Khullar S, Mandal S, et al. Cocrystals of hesperetin: structural, pharmacokinetic, and pharmaco-dynamic evaluation. Crystal Growth & Design 2017;17(5):2386-405. DOI: https://doi.org/10.1021/acs.cgd.6b01769

- Chi Z, Wang M, Yang L, Li X, Cong X, Liu S, et al. Fourier transform near-infrared spectroscopy used for purity determination of rhein-L-arginine cocrystal (argirein). Anal Sci 2013;29 (6):661-4. DOI: https://doi.org/10.2116/analsci.29.661

- Essa EA, Elbasuony AR, Abdelaziz AE, El Maghraby GM. Co-crystallization for enhanced dissol-ution rate of bicalutamide: preparation and evaluation of rapidly disintegr-ating tablets. Drug Dev Ind Pharm 2019:1-9. DOI: https://doi.org/10.1080/03639045.2019.1571504

- Lu J, Li Y-P, Wang J, Li Z, Rohani S, Ching C-B. Pharmaceutical cocrysta-ls: a comparison of sulfamerazine with sulfamethazine. J Cryst Growth 2011;335(1):110-4. DOI: https://doi.org/10.1016/j.jcrysgro.2011.09.032

- Aliev AE, Harris KD. Probing hydrogen bonding in solids using solid state NMR spectroscopy. Supramolecular Assembly via Hydro-gen Bonds I: Springer; 2004. p: 1-53. DOI: https://doi.org/10.1007/b14136

- Chierotti MR, Gobetto R. NMR crystallography: the use of dipolar interactions in polymorph and co-crystal investigation. Cryst Eng Comm 2013;15(43):8599-612. DOI: https://doi.org/10.1039/c3ce41026a

- Li Z, Matzger AJ. Influence of coformer stoichiometric ratio on pharmaceutical cocrystal dissolution: three cocrystals of carbamazepine/4-aminobenzoic acid. Mol Pharm 2016;13(3):990-5. DOI: https://doi.org/10.1021/acs.molpharmaceut.5b00843

- Lu J, Rohani S. Preparation and characterization of theophylline− nicotinamide cocrystal. Org Process Res Dev 2009;13(6):1269-75. DOI: https://doi.org/10.1021/op900047r

- Yu H, Zhang B, Liu M, Xing W, Hu K, Yang S, et al. Design, Preparation, Characterization and Evaluation of Five Cocrystal Hydrates of Flucona-zole with Hydroxybenzoic Acids. Pharmaceutics [Internet] 2022;14 (11) :2486. DOI: https://doi.org/10.3390/pharmaceutics14112486

- Saganowska P, Wesolowski M. DSC as a screening tool for rapid co-crystal detection in binary mixtures of benzodiazepines with co-formers. J Therm Anal Calorim 2018;133(1) :785-95. DOI: https://doi.org/10.1007/s10973-017-6858-3

- Schultheiss N, Newman A. Pharma-ceutical cocrystals and their physicoc-hemical properties. Crystal growth & design 2009;9(6):2950-67. DOI: https://doi.org/10.1021/cg900129f

- Chadha R, Bhandari S. Drug–excipient compatibility screening—role of thermoanalytical and spectro-scopic techniques. J Pharm Biomed 2014;87:82-97. DOI: https://doi.org/10.1016/j.jpba.2013.06.016

- Brouwers J, Brewster ME, Augustijns P. Supersaturating drug delivery systems: The answer to solubi-lity‐limited oral bioavailability? J Pharm Sci 2009;98(8):2549-72. DOI: https://doi.org/10.1002/jps.21650

- Sathisaran I, Dalvi S. Engineering cocrystals of poorly water-soluble drugs to enhance dissolution in aqueous medium. Pharmaceutics 2018 ;10(3):108. DOI: https://doi.org/10.3390/pharmaceutics10030108

- Babu NJ, Nangia A. Solubility advantage of amorphous drugs and pharmaceutical cocrystals. Crystal Growth & Design 2011;11(7):2662-79. DOI: https://doi.org/10.1021/cg200492w

- Goud NR, Khan RA, Nangia A. Modulating the solubility of sulfacetamide by means of cocrystals. Cryst Eng Comm 2014;16(26):5859-69. DOI: https://doi.org/10.1039/C4CE00103F

- Childs SL, Chyall LJ, Dunlap JT, Smolenskaya VN, Stahly BC, Stahly GP. Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. J Am Chem Soc 2004;126(41):13335-42. DOI: https://doi.org/10.1021/ja048114o

- Chow SF, Shi L, Ng WW, Leung KHY, Nagapudi K, Sun CC, et al. Kinetic entrapment of a hidden curcumin cocrystal with phlorog-lucinol. Crystal Growth & Design 2014;14(10):5079-89. DOI: https://doi.org/10.1021/cg5007007

- Kaur R, Cavanagh KL, Rodríguez-Hornedo N, Matzger AJ. Multidrug cocrystal of anticonvulsants: influence of strong intermolecular interactions on physiochemical properties. Crystal Growth & Design 2017;17(10):5012-6. DOI: https://doi.org/10.1021/acs.cgd.7b00741

- Guo M, Sun X, Chen J, Cai T, Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications, Acta Pharmaceutica Sinica B,

- Duggirala NK, Vyas A, Krzyzaniak JF, Arora KK, Suryanarayanan R. Mechanistic insight into caffeine–oxalic cocrystal dissociation in formulations: Role of excipients. Mol Pharm 2017;14(11):3879-87. DOI: https://doi.org/10.1021/acs.molpharmaceut.7b00587

- Emami S, Siahi-Shadbad M, Adibkia K, Barzegar-Jalali M. Recent advances in improving oral drug bioavailability by cocrystals. Bioim-pacts 2018;8(4):305-20. DOI: https://doi.org/10.15171/bi.2018.33

- Almansa C, Mercè R, Tesson N, Farran J, Tomàs J, Plata-Salamán CR. Co-Crystal of Tramadol hydro-chloride–Celecoxib (CTC): a novel API–API co-crystal for the treatment of pain. Crystal Growth & Design 2017;17(4):1884-92. DOI: https://doi.org/10.1021/acs.cgd.6b01848

- Bowles P, Brenek SJ, Caron Sp, Do NM, Drexler MT, Duan S, et al. Commercial route research and development for SGLT2 inhibitor candidate ertugliflozin. Org Process Res Dev 2014;18(1):66-81. DOI: https://doi.org/10.1021/op4002802

Downloads

Published

2023-05-22

How to Cite

Ameera A Radhi, Iman S Jaafar, Noor S Jaafar, & Sarah M Faisal. (2023). Pharmaceutical cocrystal and their role in improving solid state properties of active pharmaceutical ingredients. Al Mustansiriyah Journal of Pharmaceutical Sciences, 23(2), 180–195. https://doi.org/10.32947/ajps.v23i2.1019