Sublingual or buccal pharmaceutical composition

• US 5,763,476 A
• Filed: 10/11/1996
• Issued: 06/09/1998
• Est. Priority Date: 03/02/1994
• Status: Expired due to Term

• Current Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Original Assignee: Akzo Nobel N.V. (Nouryon BV)
• Inventors: Wieringa, Johannes Hubertus, Delbressine, Leonardus Petrus Carla
• Primary Examiner(s): MacMillan, Keith D.
• Application Number:
  US08/693,064
• Time in Patent Office: 606 Days
• Field of Search: 424/274, 514/410, 514/206, 514/270, 514/289, 514/315, 514/318
• US Class Current: 514/410
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• 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 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics

Abstract

The invention relates to a sublingual or buccal pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:6,7!oxepino- 4,5-c!pyrrole or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable auxiliaries suitable for use in sublingual or buccal compositions, and the use thereof for the manufacture of a sublingual or buccal pharmaceutical composition for the treatment of mental disorders, such as psychosis and schizophrenia.

Claims

1. A pharmaceutical composition comprising as a medicinally active compound:

trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz 2,3;

6,7!oxepino 4,5-c!pyrrole or a pharmaceutically acceptable salt thereof;

wherein the composition is a solid composition and disintegrates within 30 seconds in water at 37°

C.

2. The pharmaceutical composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable water-soluble or water-dispersable carrier material.

3. The pharmaceutical composition of claim 2, wherein the carrier material is partially hydrolysed gelatin.

5. The pharmaceutical composition of claim 1, wherein the composition disintegrates within 10 seconds in water at 37°

C.

6. The composition of claim 1, further comprising one or more pharmaceutically acceptable auxiliaries selected from the group consisting of hydrolyzed dextran, dextrin, mannitol, algenates, polyvinyl alcohol, polyvinyl pyrrolidine and water soluble cellulose derivatives.

4. A method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders, comprising administering sublingually or buccally an effective amount of a pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:

6,7!oxepino 4,5-c!pyrrole or a pharmaceutically acceptable salt thereof.

9. The method of claim 4, wherein the composition is a solid pharmaceutical composition which rapidly disintegrates in the mouth of a subject upon insertion into the buccal pouch or upon placement under the tongue.

10. The method of claim 4, wherein the pharmaceutical composition further comprises pharmaceutically acceptable auxiliaries selected from the group consisting of hydrolyzed dextran, dextrin, mannitol, algenates, polyvinyl alcohol, polyvinyl pyrrolidine and water soluble cellulose derivatives.

11. The method of claim 10, wherein the pharmaceutically acceptable auxiliary is partially hydrolyzed gelatin.

12. The method of claim 4 wherein the pharmaceutical composition comprises trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:

6,7!oxepino 4,5-c!pyrrole maleate, mannitol, and gelatin.

7. A pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:

6,7!oxepino 4,5-c!pyrrole or a pharmaceutically acceptable salt thereof; and

pharmaceutically acceptable auxiliaries, wherein the composition is made by the process of

a) providing an aqueous solution comprising said compound and a water soluble or water dispersable carrier material;

b) transferring the composition of a) into a mold;

c) freezing the composition in the mold; and

d) subliming the solvent by freeze-drying.

8. A pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:

6,7!oxepino 4,5-c!pyrrole maleate, mannitol, and gelatin.

13. A method for treating antihistamine and antiserotonin related diseases comprising administering sublingually or buccally an effective amount of a pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz 2,3:

6,7!oxepino 4,5-c!pyrrole or a pharmaceutically acceptable salt thereof.