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Complexation of tauro‐ and glyco‐conjugated bile salts with three neutral β‐CDs studied by ACE
Author(s) -
Holm René,
Nicolajsen Henrik V.,
Hartvig Rune A.,
Westh Peter,
Østergaard Jesper
Publication year - 2007
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200700311
Subject(s) - chemistry , bioavailability , solubility , conjugated system , hydroxylation , aqueous solution , nuclear chemistry , chromatography , stereochemistry , organic chemistry , pharmacology , polymer , enzyme , medicine
Complexation of the bile salts (BS) taurocholate, tauro‐β‐muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate common in rat, dog, and man with natural β‐CD and the chemically modified β‐CDs 2‐hydroxypropyl‐β‐CD and 2‐O‐methyl‐β‐CD was studied using mobility shift ACE. The CDs were selected due to their frequent use in preformulation and drug formulation as oral excipients for the solubilization of drug substances with low aqueous solubility. ACE was demonstrated to be a feasible and efficient technique for investigation of the interactions between BS and β‐CDs. All the investigated BS possessed affinity for the three CDs with stability constants ranging from 2×10 3 to 4×10 5 M − 1 . The requirements and assumptions related to the use of ACE for estimating high affinity stability constants were discussed. The extent and pattern of hydroxylation significantly influenced the affinity of the glyco‐ and tauro‐conjugated BS toward the β‐CDs (chenodeoxycholates >> deoxycholates > cholates) whereas the nature of the β‐CD derivatization and BS conjugation played a minor role only. The results indicate that displacement of drug substances from β‐CD inclusion complexes is likely to occur in the small intestine where BS are present potentially influencing drug bioavailability.