Fast-dissolving dosage forms for dopamine agonists

• US 6,316,027 B1
• Filed: 09/21/2000
• Issued: 11/13/2001
• Est. Priority Date: 08/18/1995
• Status: Expired due to Term

• Current Assignee: Catalent Pharma Solutions Incorporated (Catalent, Inc.), Catalent Pharma Solutions Limited (Catalent, Inc.), Catalent USA Packaging LLC (Catalent, Inc.), Catalent USA Paintball, Inc. (Catalent, Inc.), Catalent USA Woodstock, Inc. (Catalent, Inc.)
• Original Assignee: RP Scherer Technologies Incorporated (Catalent, Inc.)
• Inventors: Clarke, Anthony, Green, Richard D., Johnson, Edward Stewart
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): WARE, TODD
• Application Number:
  US09/666,173
• Time in Patent Office: 418 Days
• Field of Search: 424/464, 424/484, 424/485, 424/486, 424/488, 514/289
• US Class Current: 424/464
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

In one embodiment, this invention relates to a pharmaceutical composition for oral administration consisting essentially of a gelatin at a concentration up to 5% by weight as a carrier, a solvent, and, as an active ingredient, a dopamine agonist. Alternatively, the invention relates to a composition that takes the form of a solid, unitary fast-dispersing dosage form comprised of a network of an active ingredient after and a water-soluble or water dispersible matrix forming agent or carrier which is inert towards the active ingredient after subliming solvent from the composition in the solid state. The dosage is designed to completely disintegrate within 1 to 30 seconds of being placed in the oral cavity. Compositions which further comprise an anti-emetic and/or an opioid antagonist are also provided herein.

Claims

1. A pharmaceutical composition for oral administration consisting essentially of gelatin at a concentration of up to 5% by weight as a carrier, water, and, as an active ingredient, apomorphine or a salt thereof, characterized in that the composition is in the form of a solid, unitary fast-dispersing dosage form consisting essentially of a network of the active ingredient and the carrier which is inert towards the active ingredient after subliming said water from said composition in the solid state, and, wherein said dosage form completely disintegrates within 1 to 30 seconds of being placed in the oral cavity.

2. The pharmaceutical composition according to claim 1 comprising at least one additional carrier.

3. The composition according to claim 1 which additionally comprises at least one agent selected from the group consisting of anti-emetic agents, opioid antagonists, excipients and flavoring agents.

4. A method for the treatment of Parkinson'"'"'s disease consisting essentially of orally administering to a patient a therapeutically effective amount of a composition according to claim 1.

5. The method according to claim 4 wherein said composition additionally comprises at least one agent selected from the group comprising anti-emetic agents, opioid antagonists, excipients and flavoring agents.

6. A method for the treatment of Parkinson'"'"'s disease consisting essentially of orally administering to a patient a therapeutically effective amount of a composition according to claim 2.

7. The method according to claim 4 wherein said composition comprises at least one additional carrier.

8. A solid, fast dispersing dosage form obtained by subliming a solvent from a composition in the solid state, that composition consisting essentially of:

(a) water;

(b) at least one dopamine agonist selected from the group consisting of apomorphine, N-propanoraporphine, bromocriptine, cabergoline, lisoride, metergoline, naxagolide, pergolide, piribedil, ripinerole, terguride and quinagolide, salts and mixtures thereof;

(c) at least one matrix forming agent; and

(d) at least one agent selected from the group consisting of surfactants, preservatives, antioxidants, viscosity enhancers, coloring agents, flavoring agents, pH modifiers, sweeteners, anti-emetic agents, opioid antagonists and excipients; and

wherein said solid, fast-dispersing dosage form completely disintegrates within 1-30 seconds of being placed in the oral cavity.

9. The solid fast dispersing dosage form according to claim 8 wherein said composition consists essentially of:

(a) water;

(b) apomorphine HCl;

(c) gelatin;

(d) mannitol; and

(e) citric acid.

10. The solid, fast-dispersing dosage form according to claim 9 wherein said composition additionally comprises a sweetening agent.

11. The solid, fast-dispersing dosage form according to claim 10 wherein said composition additionally comprises a flavoring agent.

12. The solid, fast-dispersing dosage form according to claim 11 wherein said composition additionally comprises glycine.

13. The solid, fast-dispersing dosage form according to claim 9 wherein said composition additionally comprises at least one agent selected from the group consisting of anti-emetic agents, opioid antagonists, excipients and flavoring agents.

14. A solid, unitary dosage form that disintegrates within 1 to 30 seconds of being placed in the oral cavity obtainable by the process of:

(a) dispersing at least one matrix forming agent with water to prepare a dispersion/solution;

(b) adding to said dispersion/solution at least one dopamine agonist to prepare an agonist dispersion/solution;

(c) adding to said agonist dispersion/solution at least one agent selected from the group consisting of surfactants, preservatives, antioxidants, viscosity enhancers, coloring agents, flavoring agents, pH modifiers, sweeteners, anti-emetic agents, opioid antagonists and excipients to prepare a final dispersion;

(d) dispensing the final dispersion into pre-formed blister pockets and freezing the final dispersion in said blister pockets to form frozen final dispersions; and

(e) freeze-drying in a freeze dryer said frozen final dispersions to obtain said unitary dosage form.

15. The solid, unitary dosage form according to claim 14 wherein said final dispersion comprises:

(a) no more than 5% by weight gelatin;

(b) apomorphine hydrochloride;

(c) mannitol; and

(d) citric acid.