Lipid-based formulations for danazol containing a digestible surfactant, Labrafil M2125CS: in vivo bioavailability and dynamic in vitro lipolysis.
OBJECTIVE
To evaluate the use of Labrafil M2125CS as a lipid vehicle for danazol. Further, the possibility of predicting the in vivo behavior with a dynamic in vitro lipolysis model was evaluated.


METHODS
Danazol (28 mg/kg) was administered orally to rats in four formulations: an aqueous suspension, two suspensions in Labrafil M2125CS (1 and 2 ml/kg) and a solution in Labrafil M2125CS (4 ml/kg).


RESULTS
The obtained absolute bioavailabilities of danazol were 1.5 +/- 0.8%; 7.1 +/- 0.6%; 13.6 +/- 1.4% and 13.3 +/- 3.4% for the aqueous suspension, 1, 2 and 4 ml Labrafil M2125CS per kg respectively. Thus administration of danazol with Labrafil M2125CS resulted in up to a ninefold increase in the bioavailability, and the bioavailability was dependent on the Labrafil M2125CS dose. In vitro lipolysis of the formulations was able to predict the rank order of the bioavailability from the formulations, but not the absorption profile of the in vivo study.


CONCLUSIONS
The bioavailability of danazol increased when Labrafil M2125CS was used as a vehicle, both when danazol was suspended and solubilized in the vehicle. The dynamic in vitro lipolysis model could be used to rank the bioavailabilities of the in vivo data.
Larsen
Anne
A
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Holm
René
R
Pedersen
Mette Lund
ML
Müllertz
Anette
A
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003613:Danazol / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008066:Lipolysis; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013535:Suspensions
D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; D013535:Suspensions; D003613:Danazol