Hydrophobic Active Agent Compositions and Related Methods

• US 20110142945A1
• Filed: 02/17/2011
• Published: 06/16/2011
• Est. Priority Date: 12/17/2002
• Status: Abandoned Application

• Current Assignee: Lipocine Inc.
• Original Assignee: Lipocine Inc.
• Inventors: Gutke, Kathryn, Chen, Feng-Jing, Patel, Mahesh V., Venkateshwaran, Srinivasan
• Application Number:
  US13/029,989
• Publication Number:
  US 20110142945A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

Compositions and methods for providing hydrophobic active agents in a bioavailable form are disclosed and described. In one aspect of the invention, pharmaceutical composition containing a testosterone ester is provided. The composition includes a testosterone ester in both dissolved form and as undissolved particles and the dissolved form comprises at least 35 wt % of the testosterone ester present in the composition. The composition further includes a solubilizer and a stabilizer.

Claims

1. A pharmaceutical composition comprising:

a testosterone ester in both dissolved form and as undissolved particles, said dissolved form comprising at least 35 wt % of the testosterone ester present in the composition;

a solubilizer; and

a stabilizer.

2. The pharmaceutical composition of claim 1, wherein the solubilizer is selected from the group consisting of ethanol, benzyl alcohol, propylene glycol, glycerol, polyglycerol, transcutol, polyethylene glycol, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, glycofurol, 2-pyrrolidone, polyvinylpyrrolidone, tributylcitrate, acetyl triethylcitrate, triethylcitrate, ethyl oleate, triacetin, propylene glycol monoacetate, propylene glycol diacetate, dimethyl isosorbide, and mixtures thereof.

3. The pharmaceutical composition of claim 1, wherein the solubilizer is selected from the group consisting of ethanol, benzyl alcohol, propylene glycol, glycerol, polyglycerol, polyethylene glycol, polyvinylalcohol, polyvinylpyrrolidone, tributylcitrate, triethylcitrate, ethyl oleate, triacetin, and mixtures thereof.

4. The pharmaceutical composition of claim 1, wherein the solubilizer comprises about 5 wt % to about 20 wt % of the composition.

5. The pharmaceutical composition of claim 1, wherein the solubilizer comprises about 7 wt % to about 16 wt % of the composition.

6. The pharmaceutical composition of claim 1, wherein the solubilizer is present in an amount of 10 wt % to 50 wt % with respect to the testosterone ester.

7. The pharmaceutical composition of claim 1, wherein the stabilizer is selected from the group consisting of polyethoxylated fatty acids, PEG-fatty acid diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, mono- and diglycerides, glycerol esters of fatty acids, and mixtures thereof.

8. The pharmaceutical composition of claim 1, wherein the stabilizer is selected from the group consisting of polyethyoxylated castor oils, glycerol monolinoleate, glyceryl monostearate, glyceryl caprylate-caprate, glyceryl palmitic/stearic acid, and mixtures thereof.

9. The pharmaceutical composition of claim 1, wherein the stabilizer includes mixtures of polyoxyl 35 castor oil and polyoxyl 40 hydrogenated castor oil.

10. The pharmaceutical composition of claim 1, wherein the stabilizer comprises about 10 wt % to about 90 wt %.

11. The pharmaceutical composition of claim 1, wherein the testosterone ester comprises about 1 wt % to about 20 wt % of the composition.

12. The pharmaceutical composition of claim 1, wherein the composition forms an aqueous dispersion upon mixing with an aqueous medium.

13. The pharmaceutical composition of claim 12, wherein the testosterone ester is present in dissolved form and as undissolved particles in the aqueous dispersion.

14. The pharmaceutical composition of claim 12, wherein at least 20 wt % of the testosterone ester is present as undissolved particles in the aqueous dispersion.

15. The pharmaceutical composition of claim 13, wherein the aqueous dispersion of the composition provides substantially equivalent bioavailability as compared to a dispersion having only dissolved drug.

16. The pharmaceutical composition of claim 13, wherein the difference in the mean diameter measured based on volume weighed distribution of the particle and/or droplet containing the dissolved testosterone ester and the undissolved testosterone ester in the aqueous dispersion is at least about 10 nm.

17. The pharmaceutical composition of claim 1, wherein the stabilizer is substantially free of lipophilic components.

18. The pharmaceutical composition of claim 1, wherein the stabilizer is substantially free of polyoxylethylene sorbitan fatty acid ester or sorbitan fatty acid ester.

19. The pharmaceutical composition of claim 1, wherein the stabilizer is substantially free of TPGS.

20. The pharmaceutical composition of claim 1, wherein the composition further comprises a thickening agent.

21. The pharmaceutical composition of claim 1, wherein the composition is an oral dosage form.

22. The pharmaceutical composition of claim 1, wherein the oral dosage form is a soft gelatin capsule.