Eutectic systems, including eutectic salts, deep eutectic solvents, and eutectic molecular mixtures, have recently been shown to have enormous potential in a number of technological and scientific endeavors. Eutectic mixtures, along with other binary systems including solid dispersion, cocrystals, and inclusion complexes, could be used simultaneously to improve a number of drugs, including stability, permeability, and dissolution. Over the past few years, their usefulness in the pharmaceutical field has expanded. On a laboratory scale and an industrial scale, eutectics could be produced quite readily (and occasionally spontaneously). In order to fully utilize eutectics in the pharmaceutical industry, it is essential to understand their preparation process, characteristics, and evaluation criteria as well as how they affect drug dissolution.


  1. Pedro SN, Freire CS, Silvestre AJ, Freire MG. Deep Eutectic Solvents and Pharmaceuticals. Encyclopedia 2021;1(3):942e6. https://doi.org/10.3390/encyclopedia1030072.
  2. Mannu A, Blangetti M, Baldino S, Prandi C. Promising technological and industrial applications of deep eutectic systems. Materials 2021;14(10):2494. https://doi.org/10.3390/ma14102494.
  3. Atilhan M, Aparicio S. Review and perspectives for effective solutions to grand challenges of energy and fuels technologies via novel deep eutectic solvents. Energy Fuels 2021;35(8):6402e19. https://doi.org/10.1021/acs.energyfuels.1c00303.
  4. Emami S, Shayanfar A. Deep eutectic solvents for pharmaceutical formulation and drug delivery applicationsvol. 1. Pharmaceutical Development and Technology; 2020. p. 57. https://doi.org/10.1080/10837450.2020.1735414.
  5. Park CW, Mansour HM, Oh TO, Kim JY, Ha JM, Lee BJ, Chi SC, Rhee YS, Park ES. Phase behavior of itraconazoleephenol mixtures and its pharmaceutical applications. Int J Pharm 2012;436(1e2):652e8. https://doi.org/10.1016/j.ijpharm.2012.07.054.
  6. Saikia B, Seidel-Morgenstern A, Lorenz H. Multicomponent Materials to Improve Solubility: Eutectics of Drug Aminoglutethimide. Crystals 2021;12(1):40. https://doi.org/10.3390/cryst12010040.
  7. Cherukuvada S, Nangia A. Eutectics as improved pharmaceutical materials: design, properties and characterization. Chem Commun 2014;50(8):906e23. https://doi.org/10.1039/C3CC47521B.
  8. Zaini E, Wahyuni YS, Halim A, Yuliandra Y. Preparation of eutectic mixture of ketoprofen and nicotinamide for enhanced dissolution rate. Int J Pharmaceut Sci Rev Res 2015;35(1):161e4.
  9. Yu D, Xue Z, Mu T. Eutectics: formation, properties, and applications. Chemical Society Reviews; 2021. https://doi.org/10.1039/D1CS00404B.
  10. Gala U, Pham H, Chauhan H. Pharmaceutical applications of eutectic mixtures. J Dev Drugs 2013;2(3):1e2. https://doi.org/10.4172/2329-6631.1000e130.
  11. Jin Songhee, Jang Jisun, Lee Soyeon, Kim Il Won. Binary Mixtures of Some Active Pharmaceutical Ingredients with Fatty AlcoholsdThe Criteria of Successful Eutectic Formation and Dissolution Improvement. Pharmaceutics 2020;12(11):1098.https://doi.org/10.3390/pharmaceutics12111098.
  12. Smith EL, Abbott AP, Ryder KS. Eutectic Solvents (DESs) and Their Applications. Chem Rev 2014;114:11060e82.https://doi.org/10.1021/cr300162p.
  13. Avula SG, Alexander K, Riga A. Predicting eutectic behavior of drugs and excipients by unique calculations. J Therm Anal Calorim 2010;99(2):655e8.https://doi.org/10.1007/s10973-009-0595-1.
  14. Zhang Q, Vigier KD, Royer S, Jer^ome F. Deep eutectic solvents: syntheses, properties and applications. Chem Soc Rev 2012;41(21):7108e46.https://doi.org/10.1039/C2CS35178A.
  15. El Achkar T, Greige-Gerges H, Fourmentin S. Basics and properties of deep eutectic solvents: a review. Environ Chem Lett 2021;19(4):3397e408.https://doi.org/10.1007/s10311-021-01225.
  16. Sekiguchi K, Obi N. Studies on absorption of eutectic mixture I: a comparison of the behavior of a eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man.Chem Pharm Bull 1961;9:866e72.https://doi.org/10.1248/CPB.9.866.
  17. Goldberg AH, Gibaldi M, Kanig JL.Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures I: Theoretical considerations and discussion of the literature.J Pharmaceut Sci 1965;54(8):1145e8.https://doi.org/10.1002/jps.2600550610.
  18. Bazzo GC, Pezzini BR, Stulzer HK.Eutectic mixtures as an approach to enhance solubility, dissolution rate and oral bioavailability of poorly water-soluble drugs.Int J Pharm 2020;588:119741.https://doi.org/10.1016/j.ijpharm.2020. 119741.
  19. Machado SM, Castro RA, Maria TM, Canotilho J, Eusébio ME. Levetiracetamþ nonsteroidal anti-inflammatory drug binary systems: a contribution to the development of new solid dosage forms. Int J Pharm 2017;533(1):1e3. https://doi.org/10.1016/j.ijpharm.2017.09.012.
  20. Florindo C, Oliveira FS, Rebelo LP, Fernandes AM, Marrucho IM. Insights into the synthesis and properties of deep eutectic solvents based on cholinium chloride and carboxylic acids. ACS Sustainable Chem Eng 2014;2(10):2416e25. https://doi.org/10.1021/sc500439w.
  21. Haneef J, Chadha R. Drug-drug multicomponent solid forms: cocrystal, coamorphous and eutectic of three poorly soluble antihypertensive drugs using mechanochemical approach. AAPS PharmSciTech 2017;18(6):2279e90. https://doi.org/10.1208/s12249-016-0701-1.
  22. Tachibana T, Nakamura A. A method for preparing an aqueous colloidal dispersion of organic materials by using water-soluble polymers: Dispersion of В-carotene by polyvinylpyrrolidone. Kolloid-Z Z Polym 1965;203(2):130e3. https://doi.org/10.1007/BF01507758.
  23. Figueirêdo CB, Nadvorny D, de Medeiros Vieira AC, Sobrinho JL, Neto PJ, Lee PI, Soares MF. Enhancement of dissolution rate through eutectic mixture and solid solution of posaconazole and benznidazole. Int J Pharm 2017;525(1):32e42. https://doi.org/10.1016/j.ijpharm.2017.04.021.
  24. Bazzo GC, Mostafa D, França MT, Pezzini BR, Stulzer HK. How tenofovir disoproxil fumarate can impact on solubility and dissolution rate of efavirenz. Int J Pharm 2019;570:118597. https://doi.org/10.1016/j.ijpharm.2019.118597.
  25. Park H, Seo HJ, Ha ES, Hong SH, Kim JS, Kim MS, Hwang SJ. Preparation and characterization of glimepiride eutectic mixture with L-arginine for improvement of dissolution rate. Int J Pharm 2020;581:119288. https://doi.org/10.1016/j.ijpharm.2020.119288.
  26. Macasoi C, Pincu E, Jurca B, Meltzer V. Increasing the bromazepam solubility by forming a eutectic mixture with citric acid. Thermochim Acta 2021;702:178954. https://doi.org/10.1016/j.tca.2021.178954.
  27. Hyun SM, Lee BJ, Abuzar SM, Lee S, Joo Y, Hong SH, Kang H, Kwon KA, Velaga S, Hwang SJ. Preparation, characterization, and evaluation of celecoxib eutectic mixtures with adipic acid/saccharin for improvement of wettability and dissolution rate. Int J Pharm 2019;554:61e71. https://doi.org/10.1016/j.ijpharm.2018.10.044.
  28. Kim D, Jang S, Kim IW. Eutectic Formation of Naproxen with Some Dicarboxylic Acids. Pharmaceutics 2021;13:2081.https://doi.org/10.3390/pharmaceutics13122081.
  29. Parveen F, Madni A, Torchilin VP, Rehman M, Jamshaid T,Filipczak N, Rai N, Khan MM, Khan MI.Investigation of Eutectic Mixtures of Fatty Acids as a Novel Construct for Temperature-Responsive Drug Delivery.Int J Nanomed 2022;17:2413.https://doi.org/10.2147/IJN.S359664.
  30. Narwal S, Kumar A, Chaudhary M, Budhwar V.Formulation of eutectic mixture of curcumin with salicylic acid for improving its dissolution profile.Res J Pharm Technol 2021;14(4):1875e9.https://doi.org/10.52711/0974-360X.2021.00331.
  31. Law D, Wang W, Schmitt EA, Qiu Y, Krill SL, Fort JJ.Properties of rapidly dissolving eutectic mixtures of poly (ethylene glycol) and fenofibrate: the eutectic microstructure.J Pharmacol Sci 2003;92(3):505e15.https://doi.org/10.1002/jps.10324. PMID: 12587112.
  32. Wieckowski M, Królikowski M.Designing and Characterization of Low-Temperature Eutectic Phase Change Materials Based on Alkanes.J Chem Eng Data 2022;67(3):727e38.https://doi.org/10.1021/acs.jced.1c00783.
  33. Phaechamud T, Tuntarawongsa S, Charoensuksai P. Evaporation behavior and characterization of eutectic solvent and ibuprofen eutectic solution. AAPS PharmSciTech 2016;17(5):1213e20. https://doi.org/10.1208/s12249-015-0459-x.
  34. Chen Wenjun, Zhimin XUE. Investigation on the Thermal Stability of Deep Eutectic Solvents. Acta Phys Chim Sin 2018;34(8):904e11. https://doi.org/10.3866/PKU.WHXB201712281.
  35. Cherukuvada S, Guru Row TN. Comprehending the formation of eutectics and cocrystals in terms of design and their structural interrelationships. Cryst Growth 2014;14(8):4187e98. https://doi.org/10.1021/cg500790q.
  36. Hong X, Chen Z, Duffy TS. Absolute x-ray energy calibration over a wide energy range using a diffraction-based iterative method. Rev Sci Instrum 2012;83(6):063901. https://doi.org/10.1063/1.4722166.
  37. Chirawatkul P, Zeidler A, Salmon PS, Takeda SI, Kawakita Y, Usuki T, Fischer HE. Structure of eutectic liquids in the Au-Si, Au-Ge, and Ag-Ge binary systems by neutron diffraction. Phys Rev B 2011 Jan 18;83(1):014203.
  38. Pudney PDA, Mutch KJ, Zhu S. Characterising the phase behaviour of stearic acid and its triethanolamine soap and acidesoap by infrared spectroscopy. Phys Chem Chem Phys 2009;11:5010e8. https://doi.org/10.1039/B819582J.
  39. Ali HH, Ghareeb MM, Al-Remawi M, Al-Akayleh FT. New insight into single phase formation of capric acid/menthol eutectic mixtures by Fourier-transform infrared spectroscopy and differential scanning calorimetry. Trop J Pharmaceut Res 2020;19(2):361e9. https://doi.org/10.4314/tjpr.v19i2.19.
  40. Nokhodchi A, Al-Hamidi H, Antonijevic MD, Owusu-Ware S, Kaialy W. Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer. Chem Eng Res Des 2015;100:452e66. https://doi.org/10.1016/j.cherd.2015.04.018.
  41. Kumar A, Singh P, Nanda A. Hot stage microscopy and its applications in pharmaceutical characterization. Appl Microsc 2020;50(1):1. https://doi.org/10.1186/s42649-020-00032-9.
  42. Singh P, Chadha R. Depicting polymorphism in eutectic mixtures. 2022. https://doi.org/10.21203/rs.3.rs-1708945/v1.
  43. Budhwar V, Choudhary M. Pharmaceutical Eutectics: A promising drug delivery system. Res J Pharm Technol 2020;13(11):5515e23. https://doi.org/10.5958/0974-360X.2020.00963.4.
  44. Emami S, Siahi-Shadbad M, Barzegar-Jalali M, Adibkia K. Characterizing eutectic mixtures of gliclazide with succinic acid prepared by electrospray deposition and liquid assisted grinding methods. J Drug Deliv Sci Technol 2018;45:101e9.
  45. Tuntarawongsa S, Phaechamud T. Polymeric eutectic drug delivery system. J Metals Mater Miner 2012;22(2). https://doi.org/10.1016/j.jddst.2018.03.006.
  46. Domõnguez de Marõa P, Maugeri Z. Ionic liquids in biotransformations: from proof-of-concept to emerging deep eutectic solvents. Curr Opin Chem Biol 2011;15(2):220e5. https://doi.org/10.1016/j.cbpa.2010.11.008.
  47. Al-Bayati FA. Isolation and identification of antimicrobial compound from Mentha longifolia L. leaves grown wild in Iraq. Ann Clin Microbiol Antimicrob 2009;8:20. https://doi.org/10.1186/1476-0711-8-20.
  48. Chang CP, Leung TK, Lin SM, Hsu CC. Release properties on gelatin-gum arabic microcapsules containing camphor oil with added polystyrene. Colloids Surf B Biointerfaces 2006;50(2):136e40 (& Wahlgren, C.F).
  49. Wahlgren CF, Quiding H. Depth of cutaneous analgesia after application of a eutectic mixture of the local anesthetics lidocaine and prilocaine (EMLA cream). J Am Acad Dermatol 2000;42(4):584e8.
  50. Duan L, Dou LL, Guo L, Li P, Liu EH. Comprehensive evaluation of deep eutectic solvents in extraction of bioactive natural products. ACS Sustainable Chem Eng 2016;4(4):2405e11. https://doi.org/10.1021/acssuschemeng.6b00091.
  51. Bica K, Gaertner P, Rogers RD. Ionic liquids and fragrancesedirect isolation of orange essential oil. Green Chem 2011;13(8):1997e9. https://doi.org/10.1039/C1GC15237H.
  52. Pedro SN, Freire MG, Freire CS, Silvestre AJ. Deep eutectic solvents comprising active pharmaceutical ingredients in the development of drug delivery systems. Expet Opin Drug Deliv 2019;16(5):497e506. https://doi.org/10.3390/app11114897.
  53. Ferrit M, Del Valle C, Martínez F. The influence of the structural characteristics of the substrate and the medium on the stability of triflusal and acetylsalicylic acid in micellar systems. J Mol Liq 2008;142(1e3):64e71. https://doi.org/10.1016/j.molliq.2008.04.019.
  54. Briscoe CJ, Hage DS. Factors affecting the stability of drugs and drug metabolites in biological matrices. Bioanalysis 2009;1:205e20. https://doi.org/10.4155/bio.09.20.
  55. Pedro SN, Freire CS, Silvestre AJ, Freire MG. Deep Eutectic Solvents and Pharmaceuticals. Encyclopedia 2021;1(3):942e63. https://doi.org/10.3390/encyclopedia1030072.
  56. Liu Y, Friesen JB, McAlpine JB, Lankin DC, Chen SN, Pauli GF. Natural deep eutectic solvents: properties, applications, and perspectives. J Nat Prod 2018;7(813):679e90. https://doi.org/10.1007/10_2018_67.