Hydrogel and oleogel formulation of the decapeptide cetrorelix acetate for nasal administration

An oleogel and a hydrogel formulation were developed for nasal administration of the decapeptide Cetrorelix Acetate (CxAc) as non-invasive alternative to invasive routes of administration. The 2 formulations were characterised in vitro and pharmacokine-tically investigated in vivo in rats. Porous silica carriers were loaded with different peptide concentrations and formulated into the oleogel matrix consisting of castor oil, Labrafil® M 1944 CS and Aerosil® 200. In the hydrogel formulation consisting of chitosan 95/500 and poloxamer 407, CxAc was present in solubilised form. In vitro both gel formulations exhibited thixotropic behaviour as well as shear rate- and temperature-dependent viscosities. Using a newly developed adhesion test, we showed that both formulations had very good gel forming and adhesive properties. Release studies showed prolonged release over > 20 hours for the oleogel formulation. Furthermore, dependence of release kinetics on the pore diameter of the silica carrier material could be shown. The hydrogel formulation released CxAc significantly faster than the oleogel in vitro. Pharmacokinetic studies after nasal administration to male Wistar rats showed peptide absorption from both formulations over 24 hours with different kinetics (oleogel: C_max = 14.1 ± 9.9 ng/ml, t_max = 1.0 ± 0.5 h, AUC_0→24h = 33.0 ± 12.67 ng/ml; hydrogel: C_max = 10.3 ± 0.8 ng/ml, t_max = 4.0 ± 2.0 h, AUC_0→24h = 217.6 ± 8.6 ng/ml). The hydrogel formulation yielded a relatively high absolute bioavailability after nasal administration of 5.3 % compared to subcutaneous (s.c.) administration, thus making it interesting for further development.