Emulsion formulations of testosterone for nasal administration

Abstract

The nasal route has received a great deal of attention due to the many advantages of nasal delivery over parenteral administration. The male sex hormone testosterone is ineffective when administered orally due to its gut wall and first-pass metabolism. Therefore, an alternative method for delivery would he the intranasal route, if the lack of aqueous solubility can be overcome. In this study a new approach to emulsion formulations of the drug has been proposed based on the hypothesis that increased absorption is possible upon solubilization of the drug and/or prolongation of the formulation residence time in the nose. Three differently charged testosterone submicron size emulsion formulations with various zeta potentials (+24.8,-23.0 and 0.06mV) were prepared as nasal spray formulations. A dose of approximately 3.8 mg testosterone per rabbit was administered to four rabbits and the bioavailability of the emulsion formulations was assessed and compared with an i.v. formulation via solid-phase extraction, followed by an HPLC analysis method. Statistical analysis of the normalized data indicated a bioavailability of 55, 51 and 37% for positively, negatively and neutrally charged emulsions respectively. The results of this study strongly suggest that emulsion formulations have some potential to be considered for nasal delivery. Further, both the positively and negatively charged emulsion formulations provided a better bioavailability than the neutral charged emulsion, probably indicating that the charged particle interactions between emulsion globules and the mucus layer prolong the contact of drug with nasal membrane thus enhancing drug absorption.

Key Words:

• Nasal delivery
• testosterone
• emulsions
• bioavailability
• zeta potential nasal formulations