Traditional, Advanced and Green preparation methods of active pharmaceutical ingredient cocrystals: A review
Keywords:
Cocrystal, Approaches, Traditional, advanced, GreenAbstract
Pharmaceutical cocrystals are a type of solid-state modification for medicinal compounds, primarily used to improve solubility. Cocrystal engineering is an alternative technique for enhancing the solubility, dissolution, and bioavailability of drugs. Pharmaceutical cocrystals consist of multiple molecules bound together by non-covalent interaction such as hydrogen bonding, van der Waals forces, and 𝜋-𝜋 stacking. Traditionally, cocrystals have been developed through solvent evaporation, grinding, or slurry techniques, each with its own environmental limitations. The current trend in cocrystal manufacture uses more advanced and environmentally friendly methods that utilize high technology. This review provides a brief overview of each procedure for generating cocrystals in pharmaceutical area based on sustainability, energy efficiency, and environmental impact.
References
Jayram P, Sudheer P. Pharmaceutical Co-crystals: A Systematic Review. Int J Pharm Investig. 2020;10:246–52. doi.org/10.5530/IJPI.2020.3.45.
Guo M, Sun X, Chen J, Cai T. Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications. Acta Pharm Sin B. 2021;11:2537–64. doi.org/10.1016/J.APSB.2021.03.030.
Rathi R, Kaur S, Singh I. A Review on Co-crystals of Herbal Bioactives for Solubility Enhancement: Preparation Methods and Characterization Techniques. Cryst Growth Des 2022;22:2023–42. doi.org/10.1021/ACS.CGD.1C01408/ASSET/IMAGES/MEDIUM/CG1C01408_0009.GIF.
Guo M, Sun X, Chen J, Cai T. Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications. Acta Pharm Sin B. 2021;11:2537–64. doi.org/10.1016/J.APSB.2021.03.030.
Mardiyanto, Untari B, Mara A, Ferdiansyah DF. Formation of Hydroxyl-Amide Solid Dispersion Involving Azithromycin and Chitosan-Alginate Biopolymer to Increase the Dissolution Rate of Azithromycin. Science and Technology Indonesia. 2023;8:647–53. doi.org/10.26554/STI.2023.8.4.647-653.
Jafari MK, Ziaee A, O’Reilly E, Croker D, Walker G. Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters. Pharmaceutics. 2022;14:1–19. doi.org/10.3390/pharmaceutics14030634.
Chettri A, Subba A, Singh GP, Bag PP. Pharmaceutical co-crystals: A green way to enhance drug stability and solubility for improved therapeutic efficacy. Journal of Pharmacy and Pharmacology. 2024;76:1–12. doi.org/10.1093/JPP/RGAD097.
Pawar N, Saha A, Nandan N, Parambil J V. Solution Cocrystallization: A Scalable Approach for Cocrystal Production. Crystals. 2021,11(3)303. doi.org/10.3390/CRYST11030303.
Baby P, Shabaraya AR, Bhavyashree T. Pharmaceutical Cocrystals: a Novel Approach for Solubility Modification. World J Pharm Res. 2021;10:1707–24. doi.org/10.20959/wjpr20214-20205.
Dutt B, Choudhary M, Budhwar V. Cocrystallization: An Innovative Route toward Better Medication. Journal of Reports in Pharmaceutical Sciences. 2020;9(2):256–70. doi.org/10.4103/jrptps.JRPTPS_103_19.
Ngilirabanga JB, Samsodien H. Pharmaceutical co-crystal: An alternative strategy for enhanced physicochemical properties and drug synergy. Nano Select 2021;2(3):512–26. doi.org/10.1002/nano.202000201.
Baby P, Shabaraya AR. Pharmaceutical Cocrystals: A Novel Approach for Solubility Modification. World J Pharm Res 2021;10(4):1708. doi.org/10.20959/wjpr20214-20205.
Nurismi E, Rosaini H, Octavia dan MD. Review: Effect of Different Methods on the Multicomponents Crystal Formation from Medicinal Natural Ingredient Compounds. IJPSM 2021;6(5):32–9. doi.org/10.47760/IJPSM.2021.V06I05.004.
Haskins MM, Zaworotko MJ. Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods. Cryst Growth Des. 2021;21(7):4141–50. doi.org/10.1021/ACS.CGD.1C00418/ASSET/IMAGES/MEDIUM/CG1C00418_0009.GIF.
Solares-Briones M, Coyote-Dotor G, Páez-Franco JC, Zermeño-Ortega MR, Contreras CM de la O, Canseco-González D, et al. Mechanochemistry: A Green Approach in the Preparation of Pharmaceutical Cocrystals. Pharmaceutics 2021;13(6):790. doi.org/10.3390/PHARMACEUTICS13060790.
Gołdyn MR, Larowska D, Bartoszak-Adamska E. Novel Purine Alkaloid Cocrystals with Trimesic and Hemimellitic Acids as Coformers: Synthetic Approach and Supramolecular Analysis. Cryst Growth Des. 2021;21(1):396–413. doi.org/10.1021/ACS.CGD.0C01242/SUPPL_FILE/CG0C01242_SI_001.PDF.
Ying P, Yu J, Su W. Liquid-Assisted Grinding Mechanochemistry in the Synthesis of Pharmaceuticals. Adv Synth Catal. 2021;363(5):1246–71. doi.org/10.1002/adsc.202001245.
Gowda BHJ, Ahmed MG, Shankar SJ, Paul K, Chandan RS, Sanjana A, et al. Preparation and characterization of efavirenz cocrystals: An endeavor to improve the physicochemical parameters. Mater Today Proc. 2022;57(2):878–86. doi.org/10.1016/J.MATPR.2022.02.543.
Laily AP, Irawan ED, Wisudyaningsih B, Barikah KZ, Wicaksono Y. Pembentukan kokristal Ketoprofen-Urea-NaCl untuk Peningkatan Sifat Kelarutan. Journal of Agropharmacy. 2024;1:26–32.
Abdelrahman H, Essa E, Maghraby G El, Arafa M. L-Proline as Co-Crystal Forming Amino Acid for Enhanced Dissolution Rate of Lamotrigine : Development of Oral Dispersible Tablet. Indonesian Journal of Pharmacy. 2023;34:574–83.
Eesam S, Bhandaru JS, Akkinepally RR, Bobbala RK. Cocrystallization of Gliclazide with Improved Physicochemical Properties. Futur J Pharm Sci. 2021;7:1–13. doi.org/10.1186/s43094-021-00261-z.
Abdullah A, Mutmainnah, Wikantyasning ER. Cocrystals of Cefixime with Nicotinamide: Improved Solubility, Dissolution, and Permeability. Indonesian Journal of Pharmacy. 2022;33:394–400. doi.org/10.22146/ijp.2530.
Dhondale MR, Thakor P, Nambiar AG, Singh M, Agrawal AK, Shastri NR, et al. Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs. Pharmaceutics. 2023;15:189. doi.org/10.3390/PHARMACEUTICS15010189/S1.
Kumar Bandaru R, Rout SR, Kenguva G, Gorain B, Alhakamy NA, Kesharwani P, et al. Recent Advances in Pharmaceutical Cocrystals: From Bench to Market. Front Pharmacol. 2021;12:780582. doi.org/10.3389/FPHAR.2021.780582.
Sakhiya DC, Borkhataria CH. A review on advancement of cocrystallization approach and a brief on screening, formulation and characterization of the same. Heliyon. 2024;10:e29057. doi.org/10.1016/j.heliyon.2024.e29057.
Sakhiya DC, Borkhataria CH. A review on advancement of cocrystallization approach and a brief on screening, formulation and characterization of the same. Heliyon. 2024;10:e29057. doi.org/10.1016/J.HELIYON.2024.E29057.
Ahuja D, Ramisetty KA, Sumanth PK, Crowley CM, Lusi M, Rasmuson AC. Microwave assisted slurry conversion crystallization for manufacturing of new co-crystals of sulfamethazine and sulfamerazine. CrystEngComm. 2020;22:1381–94. doi.org/10.1039/C9CE01886G.
MacEachern L, Kermanshahi-Pour A, Mirmehrabi M. Supercritical carbon dioxide for pharmaceutical co-crystal production. Cryst Growth Des. 2020;20:6226–44. doi.org/10.1021/ACS.CGD.0C00571/ASSET/IMAGES/MEDIUM/CG0C00571_0008.GIF.
Urano M, Kitahara M, Kishi K, Goto E, Tagami T, Fukami T, et al. Physical characteristics of cilostazol– hydroxybenzoic acid cocrystals prepared using a spray drying method. Crystals. (Basel) 2020;10. doi.org/10.3390/cryst10040313.
Hibbard T, Shankland K, Al-Obaidi H. Evaluation of two and three fluid nozzle spray drying to prepare co-crystals of salicylic acid and caffeine with improved physicochemical properties. J Drug Deliv Sci Technol. 2023;89:105073. doi.org/10.1016/j.jddst.2023.105073.
Shao SZ, Stocker MW, Zarrella S, Korter TM, Singh A, Healy AM. In Situ Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation. Mol Pharm. 2023;20:4770–85. doi.org/10.1021/acs.molpharmaceut.3c00564.
Bandaru RK, Rout SR, Kenguva G, Gorain B, Alhakamy NA, Kesharwani P, et al. Recent Advances in Pharmaceutical Cocrystals: From Bench to Market. Front Pharmacol. 2021;12:780582. doi.org/10.3389/FPHAR.2021.780582.
Ratih H, Pamudji JS, Alatas F, Soewandhi SN. Improving telmisartan mechanical properties through the formation of telmisartan and oxalic acid co-crystal by slow evaporation and ultrasound assisted co-crystallization from solution methods. Songklanakarin Journal of Science and Technology. 2020;42:188–95. doi.org/10.14456/sjst-psu.2020.25.
Alatas F, Stiawan D, Al-Hakim NA. Solubility and Scale-Up Potency of Norfloxacin-Urea Co-Crystal Prepared by Ultrasound-Assisted Slurry Co-Crystallization Method. Borneo Journal of Pharmacy. 2023;6:158–67. doi.org/10.33084/bjop.v6i2.4173.
Alatas F, Sutarna TH, Fakhrona Salman R, Nurono Soewandhi S. Mechanical Properties Improvement of Dexibuprofen through Dexibuprofen-Caffeine Co-crystal Formation by Ultrasound assisted Solution Co-crystallization Method. Indonesian Journal of Pharmaceutical Science and Technology. 2022;9:45. doi.org/10.24198/ijpst.v1i1.34713.
Tanaka R, Duggirala NK, Hattori Y, Otsuka M, Suryanarayanan R. Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients. Mol Pharm. 2020;17:274–83. doi.org/10.1021/acs.molpharmaceut.9b01004.
Sulistyowaty MI, Setyawan D, Prameswari PPM, Susilo RJK, Amrillah T, Zaini E, et al. A Comparison Study between Green Synthesis of Microwave Irradiation and Solvent Evaporation Methods in The Formation of p-Methoxycinnamic Acid-Succinic Acid Cocrystals. Science and Technology Indonesia. 2024;9:629–36. doi.org/10.26554/sti.2024.9.3.629-636.
Sakhiya DC, Borkhataria CH. A review on advancement of cocrystallization approach and a brief on screening, formulation and characterization of the same. Heliyon. 2024;10:e29057. doi.org/10.1016/j.heliyon.2024.e29057.
Duarte Í, Andrade R, Pinto JF, Temtem M. Green production of cocrystals using a new solvent-free approach by spray congealing. Int J Pharm. 2016;506:68–78. doi.org/10.1016/J.IJPHARM.2016.04.010.
Qi L, Li C, Cheng X, Hao H, Xie C. Green Mechanochemical Preparation of Cocrystal Polymorphs: Significant Effect of Intermediates and Solvents. Cryst Growth Des. 2024;24:6196–203. doi.org/10.1021/ACS.CGD.4C00340/SUPPL_FILE/CG4C00340_SI_001.PDF.
Duarte Í, Andrade R, Pinto JF, Temtem M. Green production of cocrystals using a new solvent-free approach by spray congealing. Int J Pharm. 2016;506:68–78. doi.org/10.1016/J.IJPHARM.2016.04.010.
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