TY - JOUR
T1 - Does the Digestibility of Cyclodextrins Influence the In Vivo Absorption of Benzo[a]pyrene in Rats?
AU - Olesen, Niels E
AU - Vana, Vasiliki
AU - Holm, René
N1 - Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - An important excipient used to overcome poor solubility is cyclodextrin. However, data in the literature suggest that excessive overdosing of cyclodextrins can decrease the absorption of compounds administered with cyclodextrins, due to their lack of release from the complex. γ-Cyclodextrin is digestible in contrast to β-cyclodextrins. This could potentially limit the sensitivity toward overdose, which was evaluated using benzo[a]pyrene in this study, in which rats were administered benzo[a]pyrene and different doses of the 2 cyclodextrins. Both cyclodextrins lowered the area under the curve and therefore the absorption of benzo[a]pyrene by up to a factor of 2 when dosed in high concentrations, thus indicating that overdosing of cyclodextrins may limit the oral absorption of a compound. This limitation may be artificial because the molar ratio of benzo[a]pyrene:cyclodextrin was >1:50,000 at the concentration where a significant decrease in the absorption was observed. No difference was observed between the 2 cyclodextrins, so digestibility seemed less important. More interesting was that the decrease in absorption was relatively small when compared with literature values, suggesting that the effect of overdosing a compound with cyclodextrins was lower than anticipated.
AB - An important excipient used to overcome poor solubility is cyclodextrin. However, data in the literature suggest that excessive overdosing of cyclodextrins can decrease the absorption of compounds administered with cyclodextrins, due to their lack of release from the complex. γ-Cyclodextrin is digestible in contrast to β-cyclodextrins. This could potentially limit the sensitivity toward overdose, which was evaluated using benzo[a]pyrene in this study, in which rats were administered benzo[a]pyrene and different doses of the 2 cyclodextrins. Both cyclodextrins lowered the area under the curve and therefore the absorption of benzo[a]pyrene by up to a factor of 2 when dosed in high concentrations, thus indicating that overdosing of cyclodextrins may limit the oral absorption of a compound. This limitation may be artificial because the molar ratio of benzo[a]pyrene:cyclodextrin was >1:50,000 at the concentration where a significant decrease in the absorption was observed. No difference was observed between the 2 cyclodextrins, so digestibility seemed less important. More interesting was that the decrease in absorption was relatively small when compared with literature values, suggesting that the effect of overdosing a compound with cyclodextrins was lower than anticipated.
KW - Journal Article
U2 - 10.1016/j.xphs.2015.10.027
DO - 10.1016/j.xphs.2015.10.027
M3 - Journal article
C2 - 26886315
SN - 0022-3549
VL - 105
SP - 2698
EP - 2702
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 9
ER -