Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20

Ping Li, S. Esmail Tabibi, Samuel H Yalkowsky

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Because the ionized species is more polar than its unionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination of pH control and complexation to pH control and micellization and to pH control and cosolvency. The total aqueous solubility is expressed as the addition of the concentration of all contributing species: free un-ionized drug [D(u)], free ionized drug [D(i)], un-ionized drug micelle [D(u)M], and ionized drug micelle [D(i)M] for surfactant, and free un-ionized drug [D(u)/(c)] and free ionized drug [D(i)/(c)] for cosolvent. The equations indicate that under certain conditions the ionized species can be more important in determining the drug total solubility than the un-ionized species. Flavopiridol, a weak base, is used to test these newly generated equations. As expected, the micellar partition coefficient and solubilization power for ionized flavopiridol are both less than those of the un-ionized species. However, at acidic pH, the solubilities of the ionized drug in surfactant micelles [D(i)M] and in cosolvent-water [D(i)/(c)] are both much greater than that of the un-ionized drug. This difference is because the solubilization of the ionized drug is proportional to its aqueous solubility, and its solubility [D(i)] can be as much as 24-fold greater than that of the free un-ionized species [D(u)].

Original languageEnglish (US)
Pages (from-to)507-509
Number of pages3
JournalJournal of Pharmaceutical Sciences
Volume88
Issue number5
DOIs
StatePublished - 1999

Fingerprint

alvocidib
Polysorbates
Ethanol
Pharmaceutical Preparations
Solubility
Micelles
Surface-Active Agents
Dilatation and Curettage

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20. / Li, Ping; Tabibi, S. Esmail; Yalkowsky, Samuel H.

In: Journal of Pharmaceutical Sciences, Vol. 88, No. 5, 1999, p. 507-509.

Research output: Contribution to journalArticle

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