Compositions for conjugated estrogens and associated methods

• US 7,303,763 B2
• Filed: 09/22/2003
• Issued: 12/04/2007
• Est. Priority Date: 02/12/2001
• Status: Expired due to Term

• Current Assignee: Watson Laboratories, Inc. (Abbvie Incorporated)
• Original Assignee: Watson Laboratories, Inc. (Abbvie Incorporated)
• Inventors: Ho, Thomas
• Primary Examiner(s): Sheikh; Humera N
• Application Number:
  US10/668,104
• Publication Number:
  US 20040131683A1
• Time in Patent Office: 1,534 Days
• Field of Search: 424/474, 424/475, 424/479, 424/482
• US Class Current: 424/479
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2826 Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

Oral conjugated estrogen formulations are disclosed and described. In one aspect, the oral formulation may be a tablet having a core and one or more coatings thereon. In addition to conjugated estrogen ingredients, the core may include one or more organic excipients and one or more inorganic excipients. In one aspect, the organic excipients may include less than about 20% w/w of a cellulose ingredient, and less than about 50% w/w of a sugar ingredient. In another aspect, the inorganic excipients may include less than about 10% w/w of a calcium phosphate tribasic ingredient. In yet another aspect, the formulation does not crack when stored at about 40° C. and about 75% relative humidity for about 2 months.

Claims

1. A pharmaceutical composition in a solid oral dosage form comprising:

a core containing a therapeutically effective amount of at least one conjugated estrogen, or a component thereof, and at least one organic excipient, wherein the at least one organic excipient comprises less than about 25% w/w of a cellulose ingredient, and less than about 50% w/w of a sugar ingredient, and at least one inorganic excipient, wherein the at least one inorganic excipient comprises a calcium phosphate tribasic ingredient in an amount of less than about 20% w/w; and

a pharmaceutically acceptable coating that is free of hormones, wherein the composition does not crack when stored at 40°

C. and 75% relative humidity for about two months.

2. The pharmaceutical composition of claim 1, wherein the therapeutically effective amount of conjugated estrogen is from about 0.1 mg to about 3 mg.

3. The pharmaceutical composition of claim 2, wherein the amount is about 0.625 mg.

4. The pharmaceutical composition of claim 1, wherein the coating is a sugar coating.

5. The pharmaceutical composition of claim 1, wherein the coating is an acrylic coating.

6. The pharmaceutical composition of claim 1, wherein the sugar ingredient is present in an amount of from about 5% w/w to about 50% w/w.

7. The pharmaceutical composition of claim 1, wherein the sugar ingredient is present in an amount of from about 10% w/w to about 40% w/w.

8. The pharmaceutical composition of claim 1, wherein the sugar ingredient is present in an amount of from about 20% w/w to about 30% w/w.

9. The pharmaceutical composition of claim 1, wherein the calcium phosphate tribasic ingredient is present in amount of from about 1% w/w to about 15% w/w.

10. The pharmaceutical composition of claim 1, wherein the calcium phosphate tribasic ingredient is present in amount of from about 5% w/w to about 15% w/w.

11. The pharmaceutical composition of claim 1, wherein the calcium phosphate tribasic ingredient is present in amount of from about 1% w/w to about 10% w/w.

12. The pharmaceutical composition of claim 1, wherein the calcium phosphate tribasic ingredient is present in an amount of from about 5% w/w to about 10% w/w.

13. The pharmaceutical composition of claim 1, wherein the conjugated estrogen is of a natural origin.

14. The pharmaceutical composition of claim 1, wherein the conjugated estrogen is of a synthetic origin.

15. The pharmaceutical composition of claim 1, wherein the conjugated estrogen is a mixture of estrogenic components.

16. The pharmaceutical composition of claim 1, wherein the conjugated estrogen is an ester of an estrogen.

17. The pharmaceutical composition of claim 1, wherein the cellulose ingredient is a member selected from the group consisting of:

hydroxypropyl cellulose, carboxymethylcellulose, ethyl cellulose, methyl cellulose, salts thereof, derivatives thereof, and mixtures thereof.

18. The pharmaceutical composition of claim 17, wherein the cellulose ingredient is hydroxypropyl cellulose.

19. The pharmaceutical composition of claim 1, wherein the sugar ingredient is a member selected from the group consisting of:

sucrose, glucose, mannose, fructose, lactose, and mixtures thereof.

20. The pharmaceutical composition of claim 19, wherein the sugar ingredient is sucrose.

21. The pharmaceutical composition of claim 20, wherein the sucrose is derived from a source selected from the group consisting of:

beet sources, cane sources, starch, saccharide converted sources, polysaccharide converted sources, and mixtures thereof.

22. The pharmaceutical composition of claim 21, wherein the sucrose is derived from cane sources.