Fast-dispersing dosage form containing 5-HT1 agonists

• US 20040023948A1
• Filed: 02/26/2003
• Published: 02/05/2004
• Est. Priority Date: 03/24/1997
• Status: Abandoned Application

• 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: 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.)
• Inventors: Johnson, Edward, Green, Richard David, Lacy, Jonathan, Mallard, Nicholas
• Application Number:
  US10/375,560
• Publication Number:
  US 20040023948A1
• Time in Patent Office: Days
• US Class Current: 514/216
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/45 having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• 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

Abstract

This invention relates to a pharmaceutical composition for oral administration comprising a carrier and, as an active ingredient, a 5-HT₁ agonist, characterized in that the composition is formulated to reduce pre-systemic metabolism of said 5-HT₁ agonist. A process for preparing such a composition and the use of such a composition for the treatment of anxiety, depression, attention deficit disorder and/or panic disorders and/or as a memory enhancer are also provided.

Claims

1. A pharmaceutical composition for oral administration comprising a carrier and, as an active ingredient, a 5-HT₁ agonist, characterized in that the composition is a solid fast-dispersing dosage form which disintegrates within 1 to 10 seconds of being placed in the oral cavity, said solid fast-dispersing dosage form comprising a network of the active ingredient and a water-soluble or water-dispersible carrier which is inert toward the active ingredient, the network having been obtained by subliming solvent from a composition in the solid state.

2. A composition according to claim 1 in which the composition is formulated to promote pre-gastric absorption of said 5-HT₁ agonist.

3. A composition according to claim 1 in which the composition is formulated to promote absorption of said 5-HT₁ agonist through the buccal, sublingual, pharyngeal and/or esophageal mucous membrane.

4. A composition according to claim 1 in which the composition is formulated to promote absorption of said 5-HT₁ agonist through the stomach mucous membrane.

5. A composition according to claim 1 in which the 5-HT₁ agonist is selected from buspirone, gepirone, ipsapirone, zalospirone, umespirone, alnespirone, enilospirone, WY-48723, SUN-8399, tandospirone, flesinoxan, lesopitron, ebalzotan, adatanserin, LY-228729, F-8910-RS, U-93385, SL-87.0765, FG-5893, S-14506, EMD-56551, HT-90B, F-92502-CN, E-4414, MKC-242, F-12439, BIMT-17, LY-39, SL-88.0338, SR-57746A, LY-175644, A-74283, Bay-r-1531, CGS-12066B, CGP-50281, WAY-100012, 3a,4,4a,6a,7,7a-hexahydro-2-[4-[4-(2-pyrimidinyl)-1-[piperazinyl]butyl]-4,7-ethenocyclobuta[f]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide, cis-7-chloro-10-methoxy-5a 10b-dihydro-3N-n-propyl-6H-indeno[ 1,2-d]azepine, 1-cyclohexyl-3-[4-[4-(2,3-dihydro-2,2-dimethylbenzofuran-7-yl)-1-piperazinyl]-1-butyl]-2-imidazolidinone,1-[3-amino-2H-1-benzopyran-2-one-8-yl]piperazine, oxaflozane, RU-5031, CP-93129, naratriptan, avitriptan, rizatriptan, L-694247, IS-159, almotriptan, zolmitriptan, sumatriptan, eletriptan, VML-251, L-0076, ALX-0625, CP-122288, VS-395, L-747201, LY-334370 and salts thereof.

6. A composition according to claim 1 in which the 5-HT₁ agonist is a 5-HT_1A agonist.

7. A composition according to claim 6 in which the 5-HT₁ agonist is selected from buspirone, gepirone, ipsapirone, zalospirone, umespirone, alnespirone, enilospirone, WY-48723, SUN-8399, tandospirone and salts thereof.

8. A composition according to claim 7 in which the 5-HT₁ agonist is buspirone or a salt thereof.

9. A composition according to claim 1 in which the active ingredient is present in an amount of from 0.5 to 30% by weight of the composition.

10. A composition according to claim 1 in which the active ingredient is present in an amount of 0.25 to 50 mg.

12. A composition as defined in claim 1 for use in the treatment of anxiety.

13. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment of depression.

14. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment of Attention Deficit Disorder With or Without Hyperactivity.

15. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment of panic disorders.

16. Use of a composition as defined in claim 1 for the manufacture of a medicament for use as a memory enhancer.

17. Use of a composition as defined in claim 1 for the manufacture of a medicament for the palliative treatment of anxiety neurosis.

18. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment and/or prophylaxis of incontinence disorders.

19. Use of a composition as defined in claim 1 for the manufacture of a medicament for inducing immunosuppression and/or treating immune disorders.

20. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment of sleep apnea and/or related respiratory disorders.

21. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment for substance addiction.

22. Use of a composition as defined in claim 1 for the manufacture of a medicament for the treatment of alcohol abuse.

23. Use of a composition as defined in claim 1 for the manufacture of a medicament for the alleviation of extrapyramidal motor disorders.

11. A pharmaceutical composition for oral administration comprising a carrier, and buspirone as an active ingredient, characterized in that the composition is in the form of a solid fast-dispersing dosage form comprising a network of buspirone and a water-soluble or water-dispersible carrier which is inert towards buspirone, the network having been obtained by subliming solvent from a composition in the solid state, that composition comprising buspirone and a solution of the carrier in a solvent, wherein said solid fast-dispersing dosage form disintegrates within 1 to 10 seconds of being placed in the oral cavity.

24. Use of a fast-dispersing dosage form designed to release active ingredient within 1 to 60 seconds of being placed in the oral cavity to deliver a 5-HT₁ agonist.