Lipid-based Formulations for Danazol Containing a Digestible Surfactant, Labrafil M2125CS: In Vivo Bioavailability and Dynamic In Vitro Lipolysis

Purpose 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.

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).

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.

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. Similar content being viewed by others

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Acknowledgments Berith Friis and Gitte Frejlev Sørensen are gratefully acknowledged for their expert help with the animal studies. Mona Elstrer is acknowledged for her help with the danazol plasma analyzes, Freja Jacobsen is acknowledged for her help with solubility measurements and Tine Buskjær Nielsen for linguistic support. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Larsen, A., Holm, R., Pedersen, M.L. et al. Lipid-based Formulations for Danazol Containing a Digestible Surfactant, Labrafil M2125CS: In Vivo Bioavailability and Dynamic In Vitro Lipolysis. Pharm Res 25, 2769–2777 (2008). https://doi.org/10.1007/s11095-008-9641-0 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s11095-008-9641-0