Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the partition coefficient method.
Int J Pharm
; 542(1-2): 100-107, 2018 May 05.
Article
em En
| MEDLINE
| ID: mdl-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 11 CD-API complexes (K11,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 K11,CD values obtained by this developed method showed a good accordance with the results from other orthogonal methods.
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Base de dados:
MEDLINE
Assunto principal:
Água
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1-Octanol
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Ciclodextrinas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article