TY - JOUR
T1 - Cinnarizine food-effects in beagle dogs can be avoided by administration in a Self Nano Emulsifying Drug Delivery System (SNEDDS)
AU - Christiansen, Martin Lau
AU - Holm, Rene
AU - Kristensen, Jakob
AU - Kreilgaard, Mads
AU - Jacobsen, Jette
AU - Abrahamsson, Bertil
AU - Müllertz, Anette
N1 - Copyright © 2013. Published by Elsevier B.V.
PY - 2014/6/16
Y1 - 2014/6/16
N2 - Purpose To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. Method A conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n = 5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy®). The food-effect was evaluated by comparing Tmax, C max and Bioavailability (F) for the different formulations. Results Food effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5 times and bioavailability increased in fed state (from 20.9 ± 5.7 to 53.8 ± 30.1). Apart from an extended T max (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted = 58.1 ± 16.7, vs. 32.7 ± 11.5), (Ffed = 79.3 ± 14.7 vs. 43.7 ± 6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. Conclusion Food effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations.
AB - Purpose To elucidate if a SNEDDS approach can eliminate the food-effect on cinnarizine absorption and to, investigate if a nutritional drink, Fresubin energy, could mimic food effect in dogs for the poorly soluble compound cinnarizine. Method A conventional tablet, a SNEDDS capsule or a SNEDDS tablet, containing cinnarizine, were dosed to beagles dogs in fed or fasted state (n = 5), with a one week wash-out period between dosing. Dogs were pre-treated with pentagastrin. Fed state was induced by a nutritional drink (Fresubin Energy®). The food-effect was evaluated by comparing Tmax, C max and Bioavailability (F) for the different formulations. Results Food effect was observed on all three parameters for the conventional tablet; Tmax was delayed 2.5 times and bioavailability increased in fed state (from 20.9 ± 5.7 to 53.8 ± 30.1). Apart from an extended T max (2.5 and 3.3 times longer in fed state compared to fasted state for the SNEDDS tablets and SNEDDS capsules respectively), food effect on absorption for the SNEDDS capsules and SNEDDS tablets was not observed. The SNEDDS capsules had a higher bioavailability in both fed and fasted state compared to SNEDDS tablets (Ffasted = 58.1 ± 16.7, vs. 32.7 ± 11.5), (Ffed = 79.3 ± 14.7 vs. 43.7 ± 6.7) There were no significant differences in bioavailability between the conventional tablet in fed state and the SNEDDS capsules. Conclusion Food effect was observed when dosing cinnarizine with ingestion of the nutritional drink Fresubin Energy. Food effect on cinnarizine could be significantly reduced by dosing either as a SNEEDS capsule or a SNEDDS tablet, however, the SNEDDS tablet resulted in an overall lower absorption than the SNEDDS capsules in both fed and fasted state. The delay in fed state absorption could not be changed by dosing with SNEDDS formulations.
U2 - 10.1016/j.ejps.2013.11.003
DO - 10.1016/j.ejps.2013.11.003
M3 - Journal article
C2 - 24239996
SN - 0928-0987
VL - 57
SP - 164
EP - 172
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
ER -