Silicone based emulsions for topical drug delivery

Abstract

A water-in-oil emulsion is provided in which the lipophilic phase of the emulsion contains a silicone fluid and an emulsifier, a hydrophilic phase, and a pharmaceutically active compound. The active pharmaceutical ingredient is dissolved or dispersed in the emulsion and is partitioned in the emulsion so that all or a portion of the amount of the chemical compound dissolved or dispersed in the emulsion is dissolved or dispersed in the aqueous phase of the emulsion. The emulsion of the invention provides increased penetration into skin of the chemical compound dissolved or dispersed in the aqueous phase.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a bar chart and a line chart showing tissue distribution and penetration data in dermatomed skin for Formulations 1.1, 1.2, and 1.4 containing the API verapamil HCl (n=6, mean). The bar chart (FIG. 1A) compares the three formulations in terms of tissue distribution of the API in epidermis, dermis, and receptor medium beneath the dermis. The line chart (FIG. 1B) shows percutaneous penetration of the API from the three formulations measured in the receptor medium.

FIG. 2 is a bar chart and a line chart showing tissue distribution and penetration data in dermatomed skin for Formulations 1.1, 1.3, and 1.5 containing the API verapamil HCl (n=6, mean). The bar chart (FIG. 2A) compares the three formulations in terms of tissue distribution of the API in epidermis, dermis, and receptor medium beneath the dermis. The line chart (FIG. 2B) shows percutaneous penetration of the API from the three formulations measured in the receptor medium.

FIG. 3 is a bar chart showing % of the dose applied of an oligonucleotide from successive tape strips following application of Formulations 2.5, 2.7, and 2.9 to dermatomed skin.

FIG. 4 is a bar chart showing % of the dose applied of an oligonucleotide in epidermis and dermis following application of Formulations 2.5, 2.7, and 2.9 to dermatomed skin.

FIG. 5 is a bar chart showing % of the applied dose of ¹⁴C-Caffeine recovered from the epidermis and dermis following application of Formulations 2227-60, 2227-65, 2227-70, 2227-71, 2227-78, 2227-84, 2227-85, 2227-91, 2227-32 and 2227-33A-34 to dermatomed skin.

FIG. 6 is a bar chart showing % of the applied dose of ¹⁴C-Glucose recovered from the epidermis and dermis following application of Formulations 2227-60, 2227-70, 2227-71, 2227-84, 2227-85, 2227-32 and 2227-33A-34 to dermatomed skin.

Claims

1. A stable emulsion formulation for topical administration to the skin of a mammal, comprising an internal hydrophilic phase containing a hydrophilic solvent, a pharmaceutically active compound dissolved or dispersed in whole or in part in the hydrophilic solvent, a continuous lipophilic phase containing a silicone oil, and an emulsifier dissolved in whole or in part in the continuous phase.

2. The emulsion formulation of claim 1 wherein the hydrophilic solvent is water.

3. The emulsion formulation of claim 1 wherein the hydrophilic solvent is other than water.

4. The emulsion formulation of claim 3 wherein the hydrophilic solvent is miscible with water.

5. The emulsion formulation of claim 1 wherein the pharmaceutically active compound is hydrophilic and is dissolved essentially exclusively in the hydrophilic phase.

6. The emulsion formulation of claim 1 wherein the pharmaceutically active compound is partitioned between the hydrophilic and silicone phases.

7. The emulsion formulation of claim 1 wherein the pharmaceutically active compound is dispersed within the hydrophilic phase.

8. The emulsion formulation of claim 1 which further comprises a co-emulsifier.

9. The emulsion formulation of claim 1 wherein the silicone oil is one or more volatile silicones.

10. The emulsion formulation of claim 1 wherein the silicone oil is one or more non-volatile silicones.

11. The emulsion formulation of claim 1 wherein the silicone oil is a combination of one or more volatile silicones and one or more non-volatile silicones.

12. The emulsion formulation of claim 1 wherein the silicone oil is the major component of the continuous phase.

13. The emulsion formulation of claim 1 wherein the emulsifier is a silicone-based surfactant.

14. A method for making an emulsion formulation for topical administration to the skin of a mammal comprising combining a hydrophilic solvent, a lipophilic phase containing a silicone oil, and an emulsifier, wherein the emulsifier is soluble in the lipophilic phase, to produce a stable water-in-oil emulsion, and dissolving or dispersing a pharmaceutically active compound in the hydrophilic solvent.

15. The method of claim 14 wherein the pharmaceutically active compound is dissolved or dispersed in the hydrophilic solvent before the hydrophilic solvent is combined with the lipophilic phase.

16. The method of claim 14 wherein the hydrophilic solvent is water.

17. The method of claim 14 wherein the hydrophilic solvent is other than water.

18. The method of claim 17 wherein the hydrophilic solvent is miscible with water.

19. The method of claim 14 wherein the pharmaceutically active compound is hydrophilic and dissolves completely in the hydrophilic phase.

20. The method of claim 14 wherein the pharmaceutically active compound is hydrophobic and is dispersed in the hydrophilic phase.

21. The method of claim 14 which further comprises combining a co-emulsifier that is soluble in either or both of the hydrophilic solvent and the lipophilic phase.

22. The method of claim 14 wherein the silicone oil is one or more volatile silicones.

23. The method of claim 14 wherein the silicone oil is one or more non-volatile silicones.

24. The method of claim 14 wherein the silicone oil is a combination of one or more volatile silicones and one or more non-volatile silicones.

25. The method of claim 14 wherein the silicone oil is the major component of the lipophilic phase.

26. The method of claim 14 wherein the emulsifier is a silicone-based surfactant.

27. A method for increasing the penetration of a pharmaceutically active chemical compound through the stratum corneum of mammalian skin or for increasing the deposition of a chemical compound in human skin comprising topically administering to the skin of a mammalian subject in need thereof a stable water-in-oil emulsion formulation comprising the pharmaceutically active chemical compound and further comprising an internal hydrophilic phase containing a hydrophilic solvent in which the pharmaceutically active compound is partially or completely dissolved or dispersed, a continuous lipophilic phase containing a silicone oil, and an emulsifier dissolved in whole or in part in the continuous phase.

28. The method of claim 27 wherein the hydrophilic solvent is water.

29. The method of claim 27 wherein the hydrophilic solvent is other than water.

30. The method of claim 29 wherein the hydrophilic solvent is miscible with water.

31. The method of claim 27 wherein the pharmaceutically active compound is hydrophilic and dissolves completely in the hydrophilic phase.

32. The method of claim 27 wherein the pharmaceutically active compound is hydrophobic and is dispersed in the hydrophilic phase.

33. The method of claim 27 wherein the emulsion formulation further comprises a co-emulsifier that is dissolved in either or both of the hydrophilic solvent and the lipophilic phase.

34. The method of claim 27 wherein the silicone oil is one or more volatile silicones.

35. The method of claim 27 wherein the silicone oil is one or more non-volatile silicones.

36. The method of claim 27 wherein the silicone oil is a combination of one or more volatile silicones and one or more non-volatile silicones.

37. The method of claim 27 wherein the silicone oil is the major component of the lipophilic phase.

38. The method of claim 27 wherein the emulsifier is a silicone-based surfactant.