Progesterone administration by nasal spray in menopausal women: comparison between two different spray formulations

The aim of the study was to compare the bioavailability of progesterone dissolved in almond oil or dimethicone, and administered by nasal spray. Twenty healthy menopausal women were randomly allocated to treatment by four doses of intranasal spray either of a progesterone solution in almond oil, 2 mg/0.1 ml, corresponding to a total dose of approximately 11 mg of progesterone, or a progesterone solution in dimethicone 5 mg/0.1 ml corresponding to a total dose of approximately 28 mg of progesterone. Circulating progesterone levels were calculated at various time intervals following administration. The formulation with almond oil yielded a maximum progesterone concentration (Cmax of 3.75 ng/ml at Tmax = 60 min, and the area under the curve (AUC0-720) value was 1481.6 +/- 343. The formulation with dimethicone yielded a mean Cmax of 1.049 ng/ml at Tmax = 30 min; the AUC0-720 value was 302.06 +/- 37.5. Therefore, bioavailability of progesterone dissolved in almond oil proved to be largely superior compared to the solution in dimethicone. The crucial role of the carrier in the spray formulations is discussed; in addition to ensuring clinical safety, it must have good solubility for progesterone, be fluid enough to enable efficient 'spraying' and also must allow progesterone to be absorbed through the nasal mucosa.