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  • Title: Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the partition coefficient method.
    Author: Dargó G, Boros K, Péter L, Malanga M, Sohajda T, Szente L, Balogh GT.
    Journal: Int J Pharm; 2018 May 05; 542(1-2):100-107. PubMed ID: 29530562.
    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/wN-logPappN), 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.
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