Bioavailability of Cinnarizine in Dogs: Effect of SNEDDS Loading Level and Correlation with Cinnarizine Solubilization During In Vitro Lipolysis
- 468 Downloads
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.
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.
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.
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.
KEY WORDSbioavailability cinnarizine lipolysis oral drug delivery self-nanoemulsifying drug delivery systems
Simulated Intestinal Media
Self-Nanoemulsifying Drug Delivery System
Single Nucleotide Polymorphism
ACKNOWLEDGMENTS AND DISCLOSURES
Anne T. Larsen is thankful to AstraZeneca Pharmaceuticals (Sweden and UK) for financial and experimental support. Freja Jacobsen is greatly acknowledged for her contribution to determining the cinnarizine solubility in SIM and Anja G. Ohlsson is acknowledged for collaboration on the in vitro lipolysis experiments.
- 17.Rautio J, Humphreys JE, Webster LO, Balakrishnan A, Keogh JP, Kunta JR, et al. In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos. 2006;34:786–92.PubMedCrossRefGoogle Scholar