Revisiting the Solubility Concept of Pharmaceutical Compounds

Blaskó, Andrei; Leahy-Dios, Alana; Nelson, William O.; Austin, Steven A.; Killion, Robert B.; Visor, Gary C.; Massey, Ian J.

doi:10.1007/s007060170065

Cited by 16 publications

(8 citation statements)

References 1 publication

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“…The physical parameter that reflects the magnitude of self‐interaction between macromolecules is the second virial coefficient, B . There are a number of methods that can be used to determine B , including static light scattering (SLS), analytical ultracentrifugation, nephelometry, and membrane osmometry 3–5. Of these, the most widely used method is SLS; however, unlike proteins and other higher molecular weight species, peptides do not scatter sufficient amounts of light to make this a viable approach.…”

Section: Introductionmentioning

confidence: 99%

Second virial coefficient determination of a therapeutic peptide by self‐interaction chromatography

et al. 2006

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Self-interaction of macromolecules has been shown to play an important role in a number of physical processes, including crystallization, solubility, viscosity, and aggregation. Peptide self-interaction is not as well studied as for larger proteins, but should play an equally important role. The osmotic second virial coefficient, B, can be used to quantify peptide and protein self-interaction. B values are typically measured using static light scattering (SLS). Peptides, however, do not scatter enough light to allow such measurements. This study describes the first use of self-interaction chromatography (SIC) for the measurement of peptide B values because SIC does not have the molecular size limitations of SLS. In the present work, SIC was used to measure B for enfuvirtide, a 36-amino acid therapeutic peptide, as a function of salt concentration, salt type, and pH. B was found to correlate strongly with solubility and apparent molecular weight. In general, the solubility of enfuvirtide increases with pH from 6 to 10 and decreases as the salt concentration increases from 0 to 0.5M for three different salts. The effect of peptide concentration on B was also investigated and shown to have a significant effect, but only at high concentrations (>80 mg/mL).

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Section: Introductionmentioning

confidence: 99%

Second virial coefficient determination of a therapeutic peptide by self‐interaction chromatography

et al. 2006

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“…Comparison of values obtained at different time points can provide insight into whether the solubility values acquired are close to the thermodynamic solubility value. Although different protocols have been described by different authors (Avdeef , 2007Blasko et al 2001;Kerns 2001;Bergstrom et al 2002;Chen and Venkatesh 2004;Glomme et al 2005;Zhou et al 2007), the principles of the shake-flask solubility measurement method are wellestablished.…”

Section: Determining the Solubility Of Apis In Lipidic Excipientsmentioning

confidence: 99%

Discovering and Developing Molecules with Optimal Drug-Like Properties

Templeton¹,

Byrn²,

Haskell³

et al. 2015

AAPS Advances in the Pharmaceutical Sciences Series

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“…Aqueous solubility gives valuable indications about the biological activity of a drug, and therefore, is most important in preformulation studies. 7 Water solubility, co-solvency and partition coefficients are topics under attention in many research and development groups at companies like Mitsubishi Chemical Corporation, 1 Merck and Zeneca Pharmaceuticals, 8 Hoffmann-La Roche, 9 GlaxoWellcome, 10 and Pfizer, 11 to name a few.…”

Section: Industrial Importancementioning

confidence: 99%