Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the partition coefficient method

Gergő Dargó, Krisztina Boros, L. Péter, Milo Malanga, Tamás Sohajda, Lajos Szente, György T. Balogh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The present study was aimed to develop a medium-throughput screening technique for investigation of cyclodextrin (CD)–active pharmaceutical ingredient (API) complexes. Dual-phase potentiometric lipophilicity measurement, as gold standard technique, was combined with the partition coefficient method (plotting the reciprocal of partition coefficients of APIs as a function of CD concentration). A general equation was derived for determination of stability constants of 1:1 CD–API complexes (K1:1,CD) based on solely the changes of partition coefficients (logPo/w N-logPapp N), without measurement of the actual API concentrations. Experimentally determined logP value (−1.64) of 6-deoxy-6[(5/6)-fluoresceinylthioureido]-HPBCD (FITC-NH-HPBCD) was used to estimate the logP value (≈ −2.5 to −3) of (2-hydroxypropyl)-ß-cyclodextrin (HPBCD). The results suggested that the amount of HPBCD can be considered to be inconsequential in the octanol phase. The decrease of octanol volume due to the octanol–CD complexation was considered, thus a corrected octanol–water phase ratio was also introduced. The K1:1,CD values obtained by this developed method showed a good accordance with the results from other orthogonal methods.

Original languageEnglish
Pages (from-to)100-107
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume542
Issue number1-2
DOIs
Publication statusPublished - May 5 2018

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Cyclodextrins
Octanols
Pharmaceutical Preparations
Fluorescein-5-isothiocyanate

Keywords

  • (2-Hydroxypropyl)-ß-cyclodextrin
  • Drug-cyclodextrin complex
  • Lipophilicity measurements
  • Partition coefficient method
  • Potentiometric titration
  • Stability constant

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the partition coefficient method. / Dargó, Gergő; Boros, Krisztina; Péter, L.; Malanga, Milo; Sohajda, Tamás; Szente, Lajos; Balogh, György T.

In: International Journal of Pharmaceutics, Vol. 542, No. 1-2, 05.05.2018, p. 100-107.

Research output: Contribution to journalArticle

Dargó, Gergő ; Boros, Krisztina ; Péter, L. ; Malanga, Milo ; Sohajda, Tamás ; Szente, Lajos ; Balogh, György T. / Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the partition coefficient method. In: International Journal of Pharmaceutics. 2018 ; Vol. 542, No. 1-2. pp. 100-107.
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