Bioavailability of cinnarizine in dogs: effect of SNEDDS loading level and correlation with cinnarizine solubilization during in vitro lipolysis.
OBJECTIVE
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.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Anne T
AT
Larsen
Pernilla
P
Åkesson
Anna
A
Juréus
Lasse
L
Saaby
Ragheb
R
Abu-Rmaileh
Bertil
B
Abrahamsson
Jesper
J
Østergaard
Anette
A
Müllertz
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002936:Cinnarizine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008066:Lipolysis; D008297:Male; D012995:Solubility
D002121:Calcium Channel Blockers; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D002936:Cinnarizine