TY - JOUR
T1 - Evaluation of carboxymethyl-β-cyclodextrin with acid function
T2 - Improvement of chemical stability, oral bioavailability and bitter taste of famotidine
AU - Mady, Fatma M.
AU - Abou-Taleb, Ahmed E.
AU - Khaled, Khaled A.
AU - Yamasaki, Keishi
AU - Iohara, Daisuke
AU - Taguchi, Kazuaki
AU - Anraku, Makoto
AU - Hirayama, Fumitoshi
AU - Uekama, Kaneto
AU - Otagiri, Masaki
PY - 2010/9
Y1 - 2010/9
N2 - The objective of the present study was to evaluate the potential influence of carboxymethyl-β-cyclodextrin (CM-β-CyD) on the aqueous solubility, chemical stability and oral bioavailability of famotidine (FMT) as well as on its bitter taste. We examined the effect of the CM-β-CyD on the acidic degradation of FMT compared with that for sulfobutyl-ether-β-cyclodextrin (SBE-β-CyD). The potential use of CM-β-CyD for orally disintegrating tablets (ODTs) was evaluated in vitro and in vivo. A taste perception study was also carried out. A strong stabilizing influence of CM-β-CyD was observed against the acidic degradation, in sharp contrast to SBE-β-CyD which induced a weird destabilizing effect on FMT. 13C NMR was used to investigate the interaction mode between FMT and the 2 CyDs. In vivo study of ODTs indicated a significant increase in Cmax, AUC and oral bioavailability in the case of FMT-CM-β-CyD tablets, compared with plain drug tablets. However, no significant difference in Tmax and t1/2 was observed. CM-β-CyD complexation appears to be an acceptable strategy for enhancing the oral bioavailability of FMT owing to its dramatic effect on the aqueous solubility and chemical stability of the drug. In addition, it has a pronounced effect on masking the bitter taste of FMT.
AB - The objective of the present study was to evaluate the potential influence of carboxymethyl-β-cyclodextrin (CM-β-CyD) on the aqueous solubility, chemical stability and oral bioavailability of famotidine (FMT) as well as on its bitter taste. We examined the effect of the CM-β-CyD on the acidic degradation of FMT compared with that for sulfobutyl-ether-β-cyclodextrin (SBE-β-CyD). The potential use of CM-β-CyD for orally disintegrating tablets (ODTs) was evaluated in vitro and in vivo. A taste perception study was also carried out. A strong stabilizing influence of CM-β-CyD was observed against the acidic degradation, in sharp contrast to SBE-β-CyD which induced a weird destabilizing effect on FMT. 13C NMR was used to investigate the interaction mode between FMT and the 2 CyDs. In vivo study of ODTs indicated a significant increase in Cmax, AUC and oral bioavailability in the case of FMT-CM-β-CyD tablets, compared with plain drug tablets. However, no significant difference in Tmax and t1/2 was observed. CM-β-CyD complexation appears to be an acceptable strategy for enhancing the oral bioavailability of FMT owing to its dramatic effect on the aqueous solubility and chemical stability of the drug. In addition, it has a pronounced effect on masking the bitter taste of FMT.
KW - Carboxymethyl-β-CyD
KW - Chemical stability
KW - Famotidine
KW - Masking the bitter taste and oral disintegrating tablets
KW - Oral bioavailability
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U2 - 10.1016/j.ijpharm.2010.06.018
DO - 10.1016/j.ijpharm.2010.06.018
M3 - Article
C2 - 20600734
AN - SCOPUS:77955982135
SN - 0378-5173
VL - 397
SP - 1
EP - 8
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -