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Drug Solubility Assessment

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The ADME Encyclopedia

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Synonyms

Drug metabolism and pharmacokinetics (DMPK); Pharmacokinetics (PK); Pharmacodynamics (PD); Dimethyl sulphoxide (DMSO); Acidity dissociation equilibrium constant (Ka); Liquid chromatography (LC); Ultraviolet (UV); Mass spectrometry (MS); Chemiluminescence nitrogen detection (CLND)

Definition

In understanding how a drug behaves once dosed to a body, a drug’s solubility in an aqueous media is a key parameter in controlling the subsequent in vivo levels [1]. Many solubility methods have been developed to provide in vitro solubility measurements. These methods expose a compound to a solvent for a period of time and then determine the concentration of the dissolved compound. For what is a relatively simple experiment to perform, there are numerous experimental factors that can affect a solubility measurement and, consequently, influence drug discovery decisions to varying extents.

The Importance of Solubility to a Drug

In the scenarios where a drug’s route of administration relies...

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References

  1. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20.

    Article  CAS  Google Scholar 

  2. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44:235–49.

    Article  CAS  Google Scholar 

  3. Hill AP, Young RJ. Getting physical in drug discovery: a contemporary perspective on solubility and hydrophobicity. Drug Discov Today. 2010;15:648–55.

    Article  CAS  Google Scholar 

  4. Könczöl A, Dargó G. Brief overview of solubility methods: recent trends in equilibrium solubility measurement and predictive models. Drug Discov Today Technol. 2018;27:3–10.

    Article  Google Scholar 

  5. Wenlock M, Austin RP, Potter T, Barton P. A highly automated assay for determining the aqueous equilibrium solubility of drug discovery compounds. J Lab Autom. 2011;16:276–84.

    Article  Google Scholar 

  6. Colclough N, Wenlock MC. Interpreting physicochemical experimental data sets. J Comput Aided Mol Des. 2015;29:779–94.

    Article  CAS  Google Scholar 

  7. Elder D, Hiolm R. Aqueous solubility: simple predictive methods (in silico, in vitro and bio-relevant approaches). Int J Pharm. 2013;453:3–11.

    Article  CAS  Google Scholar 

  8. Sugano K, Okazaki A, Sugimoto S, Tavornvipas S, Omura A, Mano T. Solubility and dissolution profile assessment in drug discovery. Drug Metab Pharmacokinet. 2007;22:225–54.

    Article  CAS  Google Scholar 

  9. Hammes GG. Physical chemistry for the biological sciences. New Jersey, Hoboken: Wiley; 2007.

    Google Scholar 

  10. Brittain HG, Grant DJR, Myrdal PB. Effects of polymorphism and solid-state solvation on solubility and dissolution rate. In: Brittain HG, editor. Polymorphism in pharmaceutical solids. 2nd ed. New York: Informa Healthcare USA, Inc; 2009. p. 436–80.

    Google Scholar 

  11. Peltonem L, Strachan CJ. Degrees of order: a comparison of nanocrystal and amorphous solids for poorly soluble drugs. Int J Pharm. 2020; https://doi.org/10.1016/j.ijpharm.2020.119492.

  12. Saal C, Petereit AC. Optimizing solubility: kinetic versus thermodynamic solubility temptations and risks. Eur J Pharm Sci. 2012;47:589–95.

    Article  CAS  Google Scholar 

  13. Alelyunas YW, Liu R, Pelosi-Kilby L, Shen C. Application of a dried-DMSO rapid throughput 24-h equilibrium solubility in advancing discovery candidates. Eur J Pharm Sci. 2009;37:172–82.

    Article  CAS  Google Scholar 

  14. Shin DN, Wijnen JW, Engberts JBFN, Wakisaka A. On the origin of microheterogeneity: a mass spectrometric study of dimethyl sulfoxide-water binary mixture. J Phys Chem B. 2001;105:6759–62.

    Article  CAS  Google Scholar 

  15. Beynon RJ, Easterby JS. Buffer solutions: the basics. Oxford: Oxford University Press; 1996.

    Google Scholar 

  16. Avdeef A. Solubility of sparingly-soluble ionisable drugs. Adv Drug Deliv Rev. 2007;59:568–90.

    Article  CAS  Google Scholar 

  17. Frawley PJ, Mitchell NA, Ó’Ciardhá CT, Hutton KW. The effects of supersaturation, temperature, agitation and seed surface area on the secondary nucleation of paracetamol in ethanol solutions. Chem Eng Sci. 2012;75:183–97.

    Article  CAS  Google Scholar 

  18. Marmer DJ, Hurtubise PE. Nephelometric and turbidimetric immunoassay. In: Diamandis EP, Christopoulos TK, editors. Immunoassay. London: Academic Press Ltd; 1996. p. 363–87.

    Chapter  Google Scholar 

  19. Lucero-Borja D, Subirats X, Barbas R, Prohens R, Avdeef A, Ràfols C. Potentiometric CheqSol and standardized shake-flask solubility methods are complimentary tools in physicochemical profiling. Eur J Pharm Sci. 2020; https://doi.org/10.1016/j.ejps.2020.105305.

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Author information

Authors and Affiliations

  1. Cyprotex Discovery Ltd, Cheshire, UK

    Mark Wenlock & Philip Butler

Authors
  1. Mark Wenlock
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  2. Philip Butler
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Corresponding author

Correspondence to Mark Wenlock .

Section Editor information

  1. Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of la Plata (UNLP) - Argentinean National Council of Scientific and Technical Research (CONICET), La Plata, Buenos Aires, Argentina

    Alan Talevi

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Wenlock, M., Butler, P. (2021). Drug Solubility Assessment. In: The ADME Encyclopedia. Springer, Cham. https://doi.org/10.1007/978-3-030-51519-5_143-1

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  • DOI: https://doi.org/10.1007/978-3-030-51519-5_143-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-51519-5

  • Online ISBN: 978-3-030-51519-5

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