Dosage forms and methods for oral delivery of progesterone

• US 6,866,865 B2
• Filed: 02/24/2003
• Issued: 03/15/2005
• 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:
  US10/370,746
• Publication Number:
  US 20030143276A1
• Time in Patent Office: 750 Days
• Field of Search: 424/464, 424/465, 424/467, 424/489
• 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

Oral progesterone unit dosage forms comprising micronized progesterone and a solid polymeric carrier are provided. The dosage forms, upon oral administration, provide a therapeutically effective blood level of progesterone to a subject. The therapeutically effective blood level of progesterone may range from about 0.1 ng/ml to about 400 ng/ml. The dosage forms can be prepared for immediate as well as sustained release. The oral progesterone dosage form can be combined with an estrogen dosage form to provide combination hormone therapy.

Claims

1. In a solid oral dosage form suitable to deliver a dosage of progesterone 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 at least one solid form which contains from about 25 mg to about 500 mg micronized progesterone and a surfactant selected from the group consisting of sodium lauryl sulfate, glyceryl monooleate, sorbitan ester, docusate sodium and centrimide, said 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 solid form.

2. An oral dosage form according to claim 1, wherein said 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 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 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 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 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 solid form is a caplet.

8. A method of providing a solid oral dosage of progesterone which comprises administering to a patient an oral dosage form suitable to deliver a dosage of progesterone 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 including a solid form containing from about 25 mg to about 500 mg micronized progesterone and a surfactant selected from the group consisting of sodium lauryl sulfate, glyceryl monooleate, sorbitan ester, docusate sodium and centrimide, said 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 solid form.