Active Pharmaceutical Ingredient Ionic Liquid: A New Platform for the Pharmaceutical Industry
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 .
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...
- 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.(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.https://s3.amazonaws.com/cpsl-web/kc/pdfs/consumer-preferences-solid-oral-dosage-forms.pdf. Last accessed 17 Sept 2018
- 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.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
- 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
- 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.(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
- 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.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.http://clincalc.com/DrugStats/Top200Drugs.aspx. Last accessed 17 Sept 2018