Bioavailability of cinnarizine in dogs: effect of SNEDDS loading level and correlation with cinnarizine solubilization during in vitro lipolysis

TY - JOUR

T1 - Bioavailability of cinnarizine in dogs

T2 - effect of SNEDDS loading level and correlation with cinnarizine solubilization during in vitro lipolysis

AU - Larsen, Anne T

AU - Åkesson, Pernilla

AU - Juréus, Anna

AU - Saaby, Lasse

AU - Abu-Rmaileh, Ragheb

AU - Abrahamsson, Bertil

AU - Østergaard, Jesper

AU - Müllertz, Anette

PY - 2013/12

Y1 - 2013/12

N2 - Purpose: To investigate the effect of increasing the loading level of the poorly soluble drug cinnarizine in a self-nanoemulsifying drug delivery system (SNEDDS) both in vitro and in vivo. Methods: A fixed dose of cinnarizine was administered orally to dogs in solution in different amounts of SNEDDS vehicle. Furthermore, the SNEDDSs were characterised using the dynamic in vitro lipolysis model. Results: Statistical differences in bioavailability were not obtained between the different amounts of SNEDDS vehicle, in spite of differences in the tendency of cinnarizine to precipitate during in vitro lipolysis of the treatments. Use of the SNEDDS concept decreased the variation in cinnarizine exposure observed between dogs as compared to administering cinnarizine in an aqueous suspension. Conclusions: Optimization of SNEDDSs towards keeping the drug compound in solution upon in vitro lipolysis of the SNEDDSs may not be as important as previously suggested.

AB - Purpose: To investigate the effect of increasing the loading level of the poorly soluble drug cinnarizine in a self-nanoemulsifying drug delivery system (SNEDDS) both in vitro and in vivo. Methods: A fixed dose of cinnarizine was administered orally to dogs in solution in different amounts of SNEDDS vehicle. Furthermore, the SNEDDSs were characterised using the dynamic in vitro lipolysis model. Results: Statistical differences in bioavailability were not obtained between the different amounts of SNEDDS vehicle, in spite of differences in the tendency of cinnarizine to precipitate during in vitro lipolysis of the treatments. Use of the SNEDDS concept decreased the variation in cinnarizine exposure observed between dogs as compared to administering cinnarizine in an aqueous suspension. Conclusions: Optimization of SNEDDSs towards keeping the drug compound in solution upon in vitro lipolysis of the SNEDDSs may not be as important as previously suggested.

U2 - 10.1007/s11095-013-1145-x

DO - 10.1007/s11095-013-1145-x

M3 - Journal article

C2 - 23949249

SN - 0724-8741

VL - 30

SP - 3101

EP - 3113

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 12

ER -