Controlled release delivery system for nasal applications and method of treatment
This invention relates to a gel formulation for nasal administration of a controlled release formulation of hormones to the systemic circulation and/or to the brain. The special lipophilic or partly lipophilic system of the invention leads to higher bioavailability of the active ingredient caused by sustained scrum levels in plasma but also leads to a more favorable serum level profile. The special lipophilic or partly lipophilic system also allows for the modulation of brain functioning. The invention also relates to the nasal administration of steroid hormones for treatment of female sexual dysfunction (FSD) or female arousal disorder.
1. A pharmaceutical formulation comprising: (a) progesterone; (b) at least one lipophilic or partly lipophilic carrier present in an amount of from about 60% to about 98% by weight of the formulation; (c) at least one compound having surface tension decreasing activity present in an amount of from about 1% to about 20% by weight of the formulation; and (d) at least one viscosity regulating agent present in an amount of from about 0.5% to about 10% by weight of the formulation, wherein the formulation is formulated for intranasal administration.
2. The formulation of claim 1 , wherein the at least one lipophilic or partly lipophilic carrier is present in the formulation in an amount of from about 85% to about 95% by weight of the formulation.
3. The formulation according to claim 1 , wherein the lipophilic carrier comprises castor oil.
4. The formulation of claim 1 , wherein the at least one compound or mixture of compounds having surface tension decreasing activity is present in the formulation in an amount of from about 1% to about 5% by weight of the formulation.
5. The formulation according to claim 1 , wherein the at least one compound having surface tension decreasing activity comprises (i) at least one surfactant selected from the group consisting of lecithin, a fatty acid ester of polyvalent alcohol, a fatty acid ester of sorbitan, a fatty acid ester of polyoxyethylensorbitan, a fatty acid ester of polyoxyethylene, a fatty acid ester of sucrose, a fatty acid ester of polyglycerol, and a mixture thereof, and/or (ii) at least one humectant selected from the group consisting of sorbitol, glycerine, polyethylene glycol, macrogol glycerol fatty acid ester, and a mixture thereof.
6. The formulation according to claim 5 , wherein the at least one compound having surface tension decreasing activity comprises an oleoyl macrogolglyceride or a mixture of oleoyl macrogolglycerides.
7. The formulation of claim 1 , wherein the viscosity regulating agent is present in an amount of from about 1% to about 4% by weight of the formulation.
8. The formulation according to claim 1 , wherein said viscosity regulating agent comprises a thickener or gelling agent selected from the group consisting of cellulose, cellulose derivatives, polysaccharides, carbomers, polyvinyl alcohol, povidone, colloidal silicon dioxide, cetyl alcohols, stearic acid, beeswax, petrolatum, triglycerides, lanolin, and a mixture of two or more thereof.
9. The formulation according to claim 8 , wherein said viscosity increasing agent is colloidal silicon dioxide.
10. The formulation of claim 1 , wherein the formulation comprises:
(a) progesterone;
(b) castor oil in an amount of from about 60% to about 98% by weight of the formulation;
(c) an oleoyl macrogolglyercide or a mixture of macrogolglycerides in an amount of from about 1% to about 20% by weight of the formulation; and
(d) colloidal silicon dioxide in an amount of from about 0.5% to about 10% by weight of the formulation.
11. The formulation of claim 1 , wherein the formulation comprises:
(a) progesterone;
(b) castor oil in an amount of from about 75% to about 95% by weight of the formulation;
(c) an oleoyl macrogolglyercide or a mixture of oleoyl macrogolglycerides in an amount of from about 1% to about 5% by weight of the formulation; and
(d) colloidal silicon dioxide in an amount of from about 0.5% to about 7% by weight of the formulation.
12. The formulation of claim 1 , wherein the progesterone is present in the formulation in an amount of from 0.2% to 6% by weight of the formulation.
13. The formulation of claim 1 , wherein the progesterone is present in the formulation in an amount of from 0.2% to 4% by weight of the formulation.
14. The formulation of claim 1 , wherein the progesterone is present in the formulation in an amount of 0.2% by weight of the formulation.
15. The formulation of claim 1 , wherein the progesterone is present in the formulation in an amount of about 4% by weight of the formulation.
16. The formulation of claim 1 , wherein the progesterone is present in the formulation in an amount of about 6% by weight of the formulation.