Dosage forms and methods for oral delivery of progesterone

• US 6,544,553 B1
• Filed: 12/28/1999
• Issued: 04/08/2003
• Est. Priority Date: 12/28/1999
• Status: Expired due to Fees

• Current Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Original Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Hsia, David Chung, Ho, Thomas Chun, Weihmuller, Fredric B., Tan, Domingo Yap
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): TRAN, SUSAN T
• Application Number:
  US09/473,548
• Time in Patent Office: 1,197 Days
• Field of Search: 424/468, 424/484, 424/464, 424/465, 424/486, 424/451, 424/489, 424/457, 424/458, 424/469, 424/470, 424/452
• US Class Current: 424/465
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084

Abstract

Provided is an oral dosage form suitable to deliver a combined dosage of progesterone and which upon delivery through the gastrointestinal tract provides a blood concentration of from about 0.1 ng/ml to about 400 ng/ml progesterone; said dosage form comprising a combination that includes (a) a first solid form comprising from about 25 mg to about 500 mg micronized progesterone in a solid polyethylene glycol carrier having an average molecular weight of from about 1000 to 10,000 and constituting at least about 30% of said first solid form; and (b) a second solid form comprising an estrogen.

Claims

1. In an oral dosage form suitable to deliver a combined dosage of progesterone and an estrogen via the gastrointestinal tract, the improvement which upon oral administration provides a blood concentration of from about 0.1 ng/ml to about 400 ng/ml progesterone and comprises a combination that includes

(a) a first solid form containing from about 25 mg to about 500 mg micronized progesterone, said first solid form having been derived from the extrusion of a polymer matrix extruded from a mixture comprising micronized progesterone in a solid polyethylene glycol carrier which is a mixture of at least 10% by weight polyethylene glycol 1450, at least 30% by weight polyethylene glycol 3350 and at least 4% by weight polyethylene glycol 8000, the micronized progesterone having first been dispersed in molten polyethylene gylcol and, after cooling to a solid form, having been extruded, said mixture constituting from about 45% to about 65% weight of said first solid form;

and

(b) a second solid form which contains from about 0.25 mg to about 5 mg of estradiol.

2. An oral dosage form according to claim 1, wherein said first solid form comprises from about 0.1 to about 5.0% by weight of sodium lauryl sulfate.

3. An oral dosage form according to claim 1, wherein said first solid form comprises from about 0.1 to about 5.0% by weight of glyceryl monooleate.

4. An oral dosage form according to claim 1, wherein said first solid form comprises from about 0.1 to about 5.0% by weight of sorbitan ester.

5. An oral dosage form according to claim 1, wherein said first solid form comprises from about 0.1 to about 5.0% by weight of docusate sodium.

6. An oral dosage form according to claim 1, wherein said first solid form comprises from about 0.1 to about 5.0% by weight of cetrimide.

7. An oral dosage form according to claim 1, wherein said first solid form is a caplet and said second solid form is a tablet.

8. A method of providing an oral dosage of a combination therapy of progesterone and estradiol which comprises administering to a patient an oral dosage form suitable to deliver a combined dosage of progesterone and an estrogen via the gastrointestinal tract which upon oral administration provides a blood concentration of from about 0.1 ng/ml to about 400 ng/ml progesterone;

said dosage form comprising a combination that includes

(a) a first solid form containing from about 25 mg to about 500 mg micronized progesterone, said first solid form having been derived from the extrusion of a polymer matrix extruded from a mixture comprising micronized progesterone in a solid polyethylene glycol carrier which is a mixture of at least 10% by weight polyethylene glycol 1450, at least 30% by weight polyethylene glycol 3350 and at least 4% by weight polyethylene glycol 8000, the micronized progesterone having first been dispersed in molten polyethylene glycol and, after cooling to a solid form, having been extruded, said mixture constituting from about 45% to about 65% weight of said first solid form; and

(b) a second solid form which contains from about 0.25 mg to about 5 mg of estradiol.