A REVIEW ON ADVANCES IN PHARMACEUTICAL CO-CRYSTAL PREPARATION ROUTES, INTELLECTUAL PROPERTY PERSPECTIVE AND REGULATORY ASPECTS
DOI:
https://doi.org/10.22159/ijcpr.2022v14i5.2038Keywords:
Cocrystal, Crystal engineering, Regulatory guidelines, Intellectual property, PatentAbstract
As in recent years, due to the pervasiveness of poorly soluble APIs that demonstrates poor and erratic bioavailability, pharmaceutical cocrystal’s applicability to tailor the physicochemical properties has gained attention. Pharmaceutical cocrystal has been an exciting field of interest to researchers as this encouraged several regulatory bodies to create regulatory standards, which led to the approval of these crystals for marketing in various nations. With the upsurge in the growth of pharmaceutical cocrystals, the major concern is over the intellectual property perspective and regulatory status of cocrystals. With the new guidelines from the United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), the manufacturing and characterization of cocrystal have become less complicated. In this article, various preparation routes are mentioned along with this intellectual property perspective and regulatory perspective, including regulatory guidelines, which give an idea of whether cocrystals meet the criteria for patent eligibility and how they would change the current state of the pharmaceutical industry. Here, we also reviewed some recently approved patients on pharmaceutical crystals, which provided benefits over poor physicochemical property of drug substances and also enhanced the therapeutic effectiveness of that drugs.
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References
Brittain HG. Cocrystal systems of pharmaceutical interest: 2010. Cryst Growth Des. 2012 Feb 1;12(2):1046-54. doi: 10.1021/cg201510n.
Devne SR, Kapse VN, Ingale PL. Cocrystal: a review on pharmaceutical corystals design and preparation. World J Pharm Res. 2019 Apr 21;8(7):1936-50.
Basavoju S, Bostrom D, Velaga SP. Indomethacin–saccharin cocrystal: design, synthesis and preliminary pharmaceutical characterization. Pharm Res. 2008 Mar;25(3):530-41. doi: 10.1007/s11095-007-9394-1, PMID 17703346.
Jones W, Motherwell WDS, Trask AV. Pharmaceutical cocrystals: an emerging approach to physical property enhancement [MRS bulletin]. MRS Bull. 2006 Nov;31(11):875-9. doi: 10.1557/mrs2006.206.
Chappa P, Maruthapillai A, Voguri R, Dey A, Ghosal S, Basha MA. Drug–polymer co-crystals of dapsone and polyethylene gly col: an emerging subset in pharmaceutical co-crystals. Cryst Growth Des. 2018;18(12):7590-8. doi: 10.1021/acs.cgd.8b01397.
Jensen KT, Lobmann K, Rades T, Grohganz H. Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid, proline. Pharmaceutics. 2014;6(3):416-35. doi: 10.3390/pharmaceutics6030416, PMID 25025400.
Laitinen R, Lobmann K, Grohganz H, Strachan C, Rades T. Amino acids as co-amorphous excipients for simvastatin and glibenclamide: physical properties and stability. Mol Pharm. 2014;11(7):2381-9. doi: 10.1021/mp500107s, PMID 24852326.
Dengale SJ, Grohganz H, Rades T, Lobmann K. Recent advances in co-amorphous drug formulations. Adv Drug Deliv Rev. 2016;100:116-25. doi: 10.1016/j.addr.2015.12.009, PMID 26805787.
Löbmann K, Grohganz H, Laitinen R, Strachan C, Rades T. Amino acids as co-amorphous stabilizers for poorly water-soluble drugs-Part 1: Preparation, stability and dissolution enhancement. Eur J Pharm Biopharm. 2013;85:873-81. doi: 10.1016/j.ejpb.2013.03.014, PMID 23537574.
Song Y, Wang LY, Liu F, Li YT, Wu ZY, Yan C. Simultaneously enhancing the in vitro/in vivo performances of acetazolamide using proline as a zwitterionic coformer for cocrystallization. Cryst Eng Comm. 2019;21(19):3064-73. doi: 10.1039/C9CE00270G.
Kasten G, Grohganz H, Rades T, Lobmann K. Development of a screening method for co-amorphous formulations of drugs and amino acids. Eur J Pharm Sci. 2016;95:28-35. doi: 10.1016/j.ejps.2016.08.022, PMID 27531419.
Mishra J, Lobmann K, Grohganz H, Rades T. Influence of preparation technique on co-amorphization of carvedilol with acidic amino acids. Int J Pharm. 2018;552(1-2):407-13. doi: 10.1016/j.ijpharm.2018.09.070, PMID 30278256.
Kasten G, Lobmann K, Grohganz H, Rades T. Co-former selection for co-amorphous drug-amino acid formulations. Int J Pharm. 2019;557:366-73. doi: 10.1016/j.ijpharm.2018.12.036, PMID 30578980.
Tilborg A, Norberg B, Wouters J. Pharmaceutical salts and cocrystals involving amino acids: A brief structural overview of the state-of-art. Eur J Med Chem. 2014;74:411-26. doi: 10.1016/j.ejmech.2013.11.045, PMID 24487190.
Thipparaboina R, Kumar D, Chavan RB, Shastri NR. Multidrug co-crystals: towards the development of effective therapeutic hybrids. Drug Discov Today. 2016;21(3):481-90. doi: 10.1016/j.drudis.2016.02.001, PMID 26869329.
Thakuria R, Sarma B. Drug-drug and drug nutraceutical cocrystal/salt as an alternative medicine for combination therapy: a crystal engineering approach. Crystals. 2018;8(2):101. doi: 10.3390/cryst8020101.
Jensen KT, Lobmann K, Rades T, Grohganz H. Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid, proline. Pharmaceutics. 2014;6(3):416-35. doi: 10.3390/pharmaceutics6030416, PMID 25025400.
Brower V. Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol. 1998;16(8):728-31. doi: 10.1038/nbt0898-728, PMID 9702769.
Massaro M, Scoditti E, Carluccio MA, De Caterina R. Nutraceuticals and prevention of atherosclerosis: focus on omega-3 polyunsaturated fatty acids and mediterranean diet polyphenols. Cardiovasc Ther. 2010;28(4):e13-9. doi: 10.1111/j.1755-5922.2010.00211.x, PMID 20633019.
Pandey M, Verma RK, Saraf SA. Nutraceuticals: new era of medicine and health. Asian J Pharm Clin Res. 2010;3:11-5.
Sekhon BS. RGUHS. J Pharm Sci. 2012;2:16-25.
Munin A, Edwards Levy F. Encapsulation of natural polyphenolic compounds; a review. Pharmaceutics. 2011;3(4):793-829. doi: 10.3390/pharmaceutics3040793, PMID 24309309.
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: 10.1021/ja048114o, PMID 15479089.
Braga D, Grepioni F, Maini L, Prosperi S, Gobetto R, Chierotti MR. From unexpected reactions to a new family of ionic co-crystals: the case of barbituric acid with alkali bromides and caesium iodide. Chem Commun. 2010;46(41):7715-7. doi: 10.1039/c0cc02701d.
Ong TT, Kavuru P, Nguyen T, Cantwell R, Wojtas L, Zaworotko MJ. 2:1 cocrystals of homochiral and achiral amino acid zwitterions with Li+ salts: water-stable zeolitic and diamondoid metal-organic materials. J Am Chem Soc 2011;133(24):9224-7. doi: 10.1021/ja203002w, PMID 21612279.
Braga D, Grepioni F, Lampronti GI, Maini L, Turrina A. Co-crystals and salts obtained from dinitrogen bases and 1,2,3,4-cyclobutane tetracarboxylic acid and the use of the latter as a template for solid-state photocyclization reactions. Cryst Growth Des. 2011;12:5621-7.
Trask AV. An overview of pharmaceutical cocrystals as intellectual property. Molecular Pharmaceutics. 2007 Jun 4;4(3):301-9. doi: 10.1021/mp070001z, PMID 17477544.
Kumar A, Kumar S, Nanda A. A review about regulatory status and recent patents of pharmaceutical co-crystals. Advanced Pharmaceutical Bulletin. 2018 Aug;8(3):355-63. doi: 10.15171/apb.2018.042, PMID 30276131.
Rodrigues M, Baptista B, Lopes JA, Sarraguça MC. Pharmaceutical cocrystallization techniques. Advances and challenges. International Journal of Pharmaceutics. 2018 Aug 25;547(1-2):404-20. doi: 10.1016/j.ijpharm.2018.06.024, PMID 29890258.
Douroumis D, Ross SA, Nokhodchi A. Advanced methodologies for cocrystal synthesis. Advanced Drug Delivery Reviews. 2017 Aug 1;117:178-95. doi: 10.1016/j.addr.2017.07.008, PMID 28712924.
Friscicscic T, Jones W. Recent advances in understanding the mechanism of cocrystal formation via grinding. Crystal Growth and Design. 2009 Mar 4;9(3):1621-37. doi: 10.1021/cg800764n.
Friscic T, Childs SL, Rizvi SAA, Jones W. The role of solvent in mechanochemical and sonochemical cocrystal formation: a solubility-based approach for predicting cocrystallisation outcome. Cryst Eng Comm. 2009;11(3):418-26. doi: 10.1039/B815174A.
Delori A, Friscic T, Jones W. The role of mechanochemistry and supramolecular design in the development of pharmaceutical materials. Cryst Eng Comm. 2012;14(7):2350-62. doi: 10.1039/c2ce06582g.
Tan D, Loots L, Friscic T. Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs). Chemical Communications (Camb). 2016;52(50):7760-81. doi: 10.1039/c6cc02015a, PMID 27185190.
Trask AV, Motherwell WS, Jones W. Solvent-drop grinding: green polymorph control of cocrystallization. Chem Commun. 2004(7):890-1.
Othman MF, Anuar N, Ad Rahman S, Ahmad Taifuddin NA. Cocrystal screening of ibuprofen with oxalic acid and citric acid via the grinding method. InIOP Conference Series. IOP Conf Ser.: Mater Sci Eng. 2018 May 1;358(1):012065. doi: 10.1088/1757-899X/358/1/012065.
Karimi Jafari M, Padrela L, Walker GM, Croker DM. Creating cocrystals: a review of pharmaceutical cocrystal preparation routes and applications. Crystal Growth and Design. 2018 Aug 10;18(10):6370-87. doi: 10.1021/acs.cgd.8b00933.
Kelly AL, Gough T, Dhumal RS, Halsey SA, Paradkar A. Monitoring ibuprofen–nicotinamide cocrystal formation during solvent-free continuous cocrystallization (SFCC) using near infrared spectroscopy as a PAT tool. International Journal of Pharmaceutics. 2012 Apr 15;426(1-2):15-20. doi: 10.1016/j.ijpharm.2011.12.033, PMID 22274588.
Repka MA, Battu SK, Upadhye SB, Thumma S, Crowley MM, Zhang F, Martin C, McGinity JW. Pharmaceutical applications of hot-melt extrusion: Part II. Drug Development and Industrial Pharmacy. 2007 Jan 1;33(10):1043-57. doi: 10.1080/03639040701525627, PMID 17963112.
Walsh D, Serrano DR, Worku ZA, Madi AM, O'’Connell P, Twamley B, Healy AM. Engineering of pharmaceutical cocrystals in an excipient matrix: spray drying versus hot melt extrusion. International Journal of Pharmaceutics. 2018 Nov 15;551(1-2):241-56. doi: 10.1016/j.ijpharm.2018.09.029, PMID 30223079.
Bandari S, Nyavanandi D, Kallakunta VR, Janga KY, Sarabu S, Butreddy A, Repka MA. Continuous twin-screw granulation–an advanced alternative granulation technology for use in the pharmaceutical industry. International Journal of Pharmaceutics. 2020 Apr 30;580:119215. doi: 10.1016/j.ijpharm.2020.119215, PMID 32194206.
Rehder S, Christensen NP, Rantanen J, Rades T, Leopold CS. High-shear granulation as a manufacturing method for cocrystal granules. European Journal of Pharmaceutics and Biopharmaceutics. 2013 Nov 1;85:1019-30. doi: 10.1016/j.ejpb.2013.04.022, PMID 23685353.
Weyna DR, Shattock T, Vishweshwar P, Zaworotko MJ. Synthesis and structural characterization of cocrystals and pharmaceutical cocrystals: mechanochemistry vs slow evaporation from solution. Crystal Growth and Design. 2009 Feb 4;9(2):1106-23. doi: 10.1021/cg800936d.
Walsh D, Serrano DR, Worku ZA, Madi AM, O'’Connell P, Twamley B, Healy AM. Engineering of pharmaceutical cocrystals in an excipient matrix: Sspray drying versus hot melt extrusion. International Journal of Pharmaceutics. 2018 Nov 15;551(1-2):241-56. doi: 10.1016/j.ijpharm.2018.09.029, PMID 30223079.
Alhalaweh A, Kaialy W, Buckton G, Gill H, Nokhodchi A, Velaga SP. Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization performance. APS PharmSciTech. 2013 Mar;14(1):265-76. doi: 10.1208/s12249-012-9883-3, PMID 23297166.
Li D, Li J, Deng Z, Zhang H. Piroxicam–clonixin drug-drug cocrystal solvates with enhanced hydration stability. Cryst Eng Comm. 2019;21(28):4145-9. doi: 10.1039/C9CE00666D.
Yang J, Hong B, Wang N, Li X, Huang X, Bao Y, Xie C, Hao H. Thermodynamics and molecular mechanism of the formation of the cocrystals of p-hydroxybenzoic acid and glutaric acid. Cryst Eng Comm. 2019;21(42):6374-81. doi: 10.1039/C9CE01092K.
Machado TC, Kuminek G, Cardoso SG, Rodriguez Hornedo N. The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation. European Journal of Pharmaceutical Sciences. 2020 Sep 1;152:105422. doi: 10.1016/j.ejps.2020.105422, PMID 32531350.
Holan J, Ridvan L, Billot P, Stepanek F. Design of co-crystallization processes with regard to particle size distribution. Chemical Engineering Science. 2015 May 25;128:36-43. doi: 10.1016/j.ces.2015.01.045.
Barikah KZ. Traditional and novel methods for cocrystal formation: A mini-review. SRP. 2018;9(1):79-82. doi: 10.5530/srp.2018.1.15.
Padrela L, Rodrigues MA, Tiago J, Velaga SP, Matos HA, de Azevedo EG. Insight into the mechanisms of cocrystallization of pharmaceuticals in supercritical solvents. Crystal Growth and Design. 2015 Jul 1;15(7):3175-81. doi: 10.1021/acs.cgd.5b00200.
Cuadra IA, Martinez Casado FJ, Cheda JAR, Redondo MI, Pando C, Cabanas A. Production and characterization of a new copper (II) propanoate-isonicotinamide adduct obtained via slow evaporation and using supercritical CO2 as an antisolvent. Crystal Growth and Design. 2019 Jan 9;19(2):620-9. doi: 10.1021/acs.cgd.8b01034.
Mullers KC, Paisana M, Wahl MA. Simultaneous formation and micronization of pharmaceutical cocrystals by the rapid expansion of supercritical solutions (RESS). Pharmaceutical Research. 2015 Feb;32(2):702-13. doi: 10.1007/s11095-014-1498-9, PMID 25213775.
Pando C, Cabannas 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: 10.1039/C6RA10917A.
Douroumis D, Ross SA, Nokhodchi A. Advanced methodologies for cocrystal synthesis. Advanced Drug Delivery Reviews. 2017 Aug 1;117:178-95. doi: 10.1016/j.addr.2017.07.008, PMID 28712924.
Rajendran MA, Allada R, Sajid SS. Co-crystals for generic pharmaceuticals: an outlook on solid oral dosage formulations. Recent Advances in Drug Delivery and Formulation: Formerly. Recent Patents on Drug Delivery and Formulation. 2021 Mar 1;15(1):15-36.
Kumar A, Kumar S, Nanda A. A review about regulatory status and recent patents of pharmaceutical co-crystals. Advanced Pharmaceutical Bulletin. 2018 Aug;8(3):355-63. doi: 10.15171/apb.2018.042, PMID 30276131.
Datta S, Grant DJ. Crystal structures of drugs: advances in determination, prediction and engineering. Nature Reviews Drug Discovery. 2004 Jan;3(1):42-57. doi: 10.1038/nrd1280, PMID 14708020.
Almarsson OO, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chemical Communications (Camb). 2004;17(17):1889-96. doi: 10.1039/b402150a, PMID 15340589.
Trask AV. An overview of pharmaceutical cocrystals as intellectual property. Molecular Pharmaceutics. 2007 Jun 4;4(3):301-9. doi: 10.1021/mp070001z, PMID 17477544.
Desiraju GR. Pharmaceutical salts and co-crystals: retrospect and prospects. Pharmaceutical Salts and Co-Crystals. Cambridge: Royal Society of Chemistry Publishing. 2011 Nov 4:1-8.
DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R and D costs. Journal of Health Economics. 2016 May 1;47:20-33. doi: 10.1016/j.jhealeco.2016.01.012, PMID 26928437.
Kavanagh ON, Albadarin AB, Croker DM, Healy AM, Walker GM. Maximising success in multidrug formulation development: a review. Journal of Controlled Release. 2018 Aug 10;283:1-91-119. doi: 10.1016/j.jconrel.2018.05.024, PMID 29802867.
Guidance for Industry: Regulatory classification of pharmaceutical co-crystals. Center for drug evaluation and research, United States Food and Drug Administration. Available from: https://www.fda.gov/downloads/Drugs/ Guidances/UCM281764.pdf. [Last Accessed on 05 Jan 2018]
O’ Nolan D, Perry ML, Zaworotko MJ. Chloral hydrate polymorphs and cocrystal revisited: solving two cold pharmaceutical cases. Crystal Growth and Design. 2016 Apr 6;16(4):2211-7. doi: 10.1021/acs.cgd.6b00032.
Brittain HG. Pharmaceutical cocrystals: the coming wave of new drug substances. Journal of Pharmaceutical Sciences. 2013 Feb 1;102(2):311-7. doi: 10.1002/jps.23402, PMID 23192888.
Kavanagh ON, Croker DM, Walker GM, Zaworotko MJ. Pharmaceutical cocrystals: from serendipity to design to application. Drug Discovery Today. 2019 Mar 1;24(3):796-804. doi: 10.1016/j.drudis.2018.11.023, PMID 30521935.
Gediya PA, Sen DJ. Cocrystallisation technology: A magic bullet in medicinal chemistry. International Journal of Advances in Pharmaceutical Research. 2013;4(8):2071-6.
Davis RE, Lorimer KA, Wilkowski MA, Rivers JH, Wheeler KA, Bowers J. Studies of phase relationships in cocrystal systems. Cryst Supramol Chem. 2004 Jul 17;39:41-61.
Karagianni A, Malamatari M, Kachrimanis K. Pharmaceutical cocrystals: Nnew solid-phase modification approaches for the formulation of APIs. Pharmaceutics. 2018 Jan 25;10(1):18. doi: 10.3390/pharmaceutics10010018, PMID 29370068.
Bolla G, Nangia A. Pharmaceutical cocrystals: walking the talk. Chemical Communications (Camb). 2016;52(54):8342-60. doi: 10.1039/c6cc02943d, PMID 27278109.
Raheem Thayyil AR, Juturu T, Nayak S, Kamath S. Pharmaceutical co-crystallization: regulatory aspects, design, characterization, and applications. Advanced Pharmaceutical Bulletin. 2020 Jun;10(2):203-12. doi: 10.34172/apb.2020.024, PMID 32373488.
Douroumis D, Ross SA, Nokhodchi A. Advanced methodologies for cocrystal synthesis. Advanced Drug Delivery Reviews. 2017 Aug 1;117:178-95. doi: 10.1016/j.addr.2017.07.008, PMID 28712924.
Shaikh R, Singh R, Walker GM, Croker DM. Pharmaceutical cocrystal drug products: an outlook on product development. Trends in Pharmacological Sciences. 2018 Dec 1;39(12):1033-48. doi: 10.1016/j.tips.2018.10.006, PMID 30376967.
EMA. European Medicines Agency policy on the handling of competing interests of scientific committees’ members and experts. Eur Med (Agency). 2015;44:1-10.
Garg U, Azim Y. Challenges and opportunities of pharmaceutical cocrystals: a focused review on non-steroidal anti-inflammatory drugs. RSC Medicinal Chemistry. 2021;12(5):705-21. doi: 10.1039/d0md00400f, PMID 34124670.
Kuminek G, Cavanagh KL, da Piedade MFM, Rodriguez Hornedo N. Posaconazole cocrystal with superior solubility and dissolution behavior. Crystal Growth and Design. 2019 Oct 14;19(11):6592-602. doi: 10.1021/acs.cgd.9b01026.
FDA. Regulatory classification of pharmaceutical co-crystal guidance for industry; 2018.
Izutsu KI, Koide T, Takata N, Ikeda Y, Ono M, Inoue M, Fukami T, Yonemochi E. Characterization and quality control of pharmaceutical cocrystals. Chemical and Pharmaceutical Bulletin (Tokyo). 2016;64(10):1421-30. doi: 10.1248/cpb.c16-00233, PMID 27319284.
Herrera LB, Sande Lopez DDE, Lopez RP, Barbas Canero R. Cocrystals of ubiquinol and compositions comprising them. European; 2020.
Mei X, Wang J, Qihui Yu. Cocrystal of telmisartan and hydrochlorothiazide; 2020.
Ke W, Qianliu C, ZongguiGeng W, Gang YW, Xun Z. Memantine paroxetine cocrystal salt and its preparation method, pharmaceutical composition and application ther of. China; 2021.
Lee JG, Si-jun Kim JyJ, Lee JH, Jae-heon J. Young-Gil. Novel crystalline varenicline oxalate hydrate, preparation method thereof, and pharmaceutical composition comprising same. Korian Patient 20160126697A; 2016.
David T, Schultheiss JA. L-pipecolic acid cocrystal of cannabidiol. US patient 201962806318P; 2020.
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