Encyclopedia of Ionic Liquids

Living Edition
| Editors: Suojiang Zhang

Active Pharmaceutical Ingredient Ionic Liquid: A New Platform for the Pharmaceutical Industry

  • Hemant Choudhary
  • Kai Li
  • Robin D. RogersEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-981-10-6739-6_3-1

Introduction

An active pharmaceutical ingredient (API) is the primary biologically active component of a medical drug formulation that is responsible for the therapeutic effect. In ancient times, when the molecular structure and identity of the APIs were unknown, remedies composed of plants, animal by-products, and even minerals were utilized to heal, treat, and prevent the spread of disease. With the advancement of civilization, the field of medicine made fast progress, and APIs were synthesized rather being extracted from natural sources. Aspirin is generally considered the first synthetic drug, although others describe chloral hydrate as the first synthetic drug in medical history [1].

The pharmacokinetics and pharmacodynamics of an API, which are influenced by their structure, mostly govern the therapeutic efficiency, and owing to this, APIs have various chemical functional groups. These functional groups are usually capable of forming strong inter-/intramolecular interactions via...

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References

  1. 1.
    Jones AW (2011) Early drug discovery and the rise of pharmaceutical chemistry. Drug Testing and Analysis 3:337–344CrossRefGoogle Scholar
  2. 2.
    (a) Heinrich SP, Wermuth CG (eds) (2008) Handbook of pharmaceutical salts; properties, selection, and use. VHCA, Verlag Helvetica Chimica Acta, Zürich, Switzerland, and Wiley-VCH, Weinheim, Germany; (b) Shamshina JL, Kelley SP, Gurau G, Rogers RD (2015) Develop ionic liquid drugs. Nature 12:188–189Google Scholar
  3. 3.
    (a) Hough WL, Smiglak M, Rodriguez H et al (2007) The third evolution of ionic liquids: active pharmaceutical ingredients. New J Chem 31:1429–1436; (b) Shamshina JL, Berton P, Wang H et al (2017) Ionic liquids in pharmaceutical industry. In Zhang W, Cue BW (eds) Green techniques for organic synthesis and medicinal chemistry, 2nd ednGoogle Scholar
  4. 4.
  5. 5.
    (a) Stoimenovski J, MacFarlane DR, Bica K et al (2010) Crystalline vs. ionic liquid salt forms of active pharmaceutical ingredients: a position paper. Pharm Res 27:521–526; (b) Shamshina JL, Barber PS, Rogers RD (2013) Ionic liquids in drug delivery. Expert Opin Drug Deliv 10:1367–1381; (c) Egorova KS, Gordeev EG, Ananikov VP (2017) Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem Rev 117:7132–7189Google Scholar
  6. 6.
    Rogers RD, Daly DT, Swatloski RP et al (2007) Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients. US 20070093462 A1Google Scholar
  7. 7.
    Martins ICB, Oliveira MC, Diogo HP et al (2017) MechanoAPI-ILs: pharmaceutical ionic liquids obtained through mechanochemical synthesis. ChemSusChem 10:1360–1363CrossRefGoogle Scholar
  8. 8.
    Dean PM, Turanjanin J, Yoshizawa-Fujita M et al (2008) Exploring an anti-crystal engineering approach to the preparation of pharmaceutically active ionic liquids. Cryst Growth Des 9:1137–1145CrossRefGoogle Scholar
  9. 9.
    Bica K, Rogers RD (2010) Confused ionic liquid ions – a “liquification” and dosage strategy for pharmaceutically active salts. Chem Commun 46:1215–1217CrossRefGoogle Scholar
  10. 10.
    Chatel G, Pereira JFB, Debbeti V et al (2014) Mixing ionic liquids – “simple mixtures” or “double salts”? Green Chem 16:2051–2083CrossRefGoogle Scholar
  11. 11.
    Cojocaru OA, Bica K, Gurua G et al (2013) Prodrug ionic liquids: functionalizing neutral active pharmaceutical ingredients to take advantage of the ionic liquid form. MedChemComm 4:559–563CrossRefGoogle Scholar
  12. 12.
    (a) Smith DJ, Shah JK, Maginn EJ (2015) Molecular dynamics simulation study of the association of lidocainium docusate and its derivatives in aqueous solution. Mol Pharm 12:1893–1901; (b) Hough-Troutman WL, Smiglak M, Griffin S et al (2009) Ionic liquids with dual biological function: sweet and anti-microbial hydrophobic quaternary ammonium-based salts. New J Chem 33:26–33; (c) Ferraz R, Costa-Rodrigues J, Fernandes MH et al (2015) Antitumor activity of ionic liquids based on ampicillin. ChemMedChem 10:1480–1483; (d) Araujo JMM, Florindo C, Pereiro AB et al (2014) Cholinium-based ionic liquids with pharmaceutically active anions. RSC Adv 4:28126–28132; (e) Ferraz R, Noronha J, Murtinheira F et al (2016) Primaquine-based ionic liquids as a novel class of antimalarial hits. RSC Adv 6:56134–56138Google Scholar
  13. 13.
    Moniruzzamman M, Tahara Y, Tamura M et al (2010) Ionic liquid-assisted transdermal delivery of sparingly soluble drug. Chem Commun 46:1452–1454CrossRefGoogle Scholar
  14. 14.
    Stoimenovski J, MacFarlane DR (2011) Enhanced membrane transport of pharmaceutically active protic ionic liquids. Chem Commun 47:11429–11431CrossRefGoogle Scholar
  15. 15.
    (a) Wang H, Gurau G, Shamshina J et al (2014) Simultaneous membrane transport of two active pharmaceutical ingredients by charge assisted hydrogen bond complex formation. Chem Sci 5:3449–3456; (b) Berton P, Di Bona KR, Yancey D et al (2017) Transdermal bioavailability in rats of lidocaine in the forms of ionic liquids, salts, and deep eutectic. ACS Med Chem Lett 8:498–503Google Scholar
  16. 16.
    (a) Shadid M, Gurau G, Shamshina JL et al (2015) Sulfasalazine in ionic liquid form with improved solubility and exposure. MedChemComm 6:1837–1841; (b) Carrera GVSM, Santos MM, Costa A et al (2017) Highly water soluble room temperature superionic liquids of APIs. New J Chem 41:6986–6990CrossRefGoogle Scholar
  17. 17.
    Bica K, Rodriguez H, Gurau G et al (2012) Pharmaceutically active ionic liquids with solids handling, enhanced thermal stability, and fast release. Chem Commun 48:5422–5424CrossRefGoogle Scholar
  18. 18.
    For example, see, (a) Pernak J, Niemczak M, Chrzanowski L et al (2016) Betaine and carnitine derivatives as herbicidal ionic liquids. Chem Eur J 22:12012–12021; (b) Pernak J, Niemczak M, Zakrocka K et al (2013) Herbicidal ionic liquid with dual-function. Tetrahedron 69:8132–8136; (c) Choudhary H, Pernak J, Shamshina JL et al (2017) Two herbicides in a single compound: double salt herbicidal ionic liquids exemplified with glyphosate, dicamba, and MCPA. ACS Sustain Chem Eng 5:6261–6273Google Scholar
  19. 19.
    ClinicalTrials.gov (n.d.) Identifier: NCT01198834, MRX-7EAT Etodolac-lidocaine topical patch in the treatment of ankle sprains. https://clinicaltrials.gov/ct2/show/record/NCT01198834. Last accessed 17 Sept 2018
  20. 20.

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.College of Arts and SciencesThe University of AlabamaTuscaloosaUSA
  2. 2.Joint BioEnergy Institute and Sandia National LaboratoriesEmeryvilleUSA
  3. 3.525 Solutions, Inc.TuscaloosaUSA
  4. 4.Chemical Sciences DivisionOak Ridge National LaboratoryOak RidgeUSA

Section editors and affiliations

  • Zhonghao Li
    • 1
  • Maya Guncheva
  1. 1.Section 12 Emerging Applications of Ionic Liquids (Pharmacology, Food Science, Agriculture, Nuclear Science Technology, Optics)Shandong UniversityJinanChina