Evidences of cyclodextrin-mediated enantioselective photodegradation of rac-nicardipine by capillary electrophoresis.
Capillary electrophoresis (CE) was applied to photostability studies on rac-nicardipine, a dihydropyridine chiral drug. CE methods were developed able to provide the enantioresolution of drug and its separation from the photodegradation products. Enantioresolution was achieved using 5% sulfated-beta-cyclodextrin (S-beta-CD) as chiral selector in 20 mM triethanolammonium phosphate solution (pH 3). The photostability studies were carried out on inclusion complexes of rac-nicardipine with beta-cyclodextrin (beta-CD) and (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) in aqueous solutions (pH 7.4 and 5). The CE analysis of the solutions exposed to UV-A and UV-B radiations showed a photoprotective effect by beta-CD; conversely, HP-beta-CD proved to favor the drug photodegradation. Moreover, evidences for CDs-mediated stereoselective photodegradation of rac-nicardipine were obtained. In fact, two distinct photodegradation profiles were observed for the nicardipine enantiomers in the presence of the CDs. The photodegradation was found to follow an apparent first-order kinetics and two different kinetic constants (k) were obtained for the two enantiomers. After exposure to UV-A and UV-B radiations, the solutions contained residual nicardipine with a significant change in the enantiomeric ratio; this effect was depending on the CD used for the inclusion complexation.
Pomponio
R
R
Dipartimento di Scienze Farmaceutiche, Universita' di Bologna, Italy.
Gotti
R
R
Bertucci
C
C
Cavrini
V
V
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D019075:Electrophoresis, Capillary / Q000379:methods; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009529:Nicardipine / Q000737:chemistry*; D010777:Photochemistry; D012995:Solubility; D012996:Solutions; D013237:Stereoisomerism; D014466:Ultraviolet Rays; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D012996:Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009529:Nicardipine; C031215:betadex