AQUEOUS SUSPENSIONS OF SUBMICRON 9-HYDROXYRISPERIDONE FATTY ACID ESTERS

• US 20030064998A1
• Filed: 05/02/2000
• Published: 04/03/2003
• Est. Priority Date: 11/17/1997
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: FRANCOIS, MARC KAREL JOZEF, DRIES, WILLY MARIA ALBERT CARLO, BASSTANIE, ESTHER DINA GUIDO
• Granted Patent: US 6,555,544 B2
• Time in Patent Office: Days
• US Class Current: 514/259.41
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• 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
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: Y10S 977/775 Nanosized powder or flake, e.g. nanosized catalyst
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10S 977/926 Topical chemical, e.g. cosmetic or sunscreen

Abstract

The present invention is concerned with a pharmaceutical composition suitable as a depot formulation for administration via intramuscular or subcutaneous injection, comprising:

(1) as an active ingredient a therapeutically effective amount of a 9-hydroxy-risperidone fatty acid ester or a salt, or a stereoisomer or a stereoisomeric mixture thereof in submicron form and

(2) a pharmaceutically acceptable carrier; wherein the pharmaceutically acceptable carrier is water and the active ingredient is suspended therein:

and with a process of preparing such a composition.

The invention further concerns such a pharmaceutical composition for use as a medicament in the treatment of psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioural disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioural disturbances in mental retardation and autism, Tourette'"'"'s syndrome, bipolar mania, depression, anxiety.

Claims

1. A pharmaceutical composition suitable as a depot formulation for administration by intramuscular or subcutaneous injection, comprising a dispersion of particles consisting essentially of a therapeutically effective amount of a crystalline 9-hydroxyrisperidone fatty acid ester having the formula

2. A composition according to claim 1 wherein R represents a straight C₁₅ (pentadecyl) chain and the active ingredient is 9-hydroxyrisperidone palmitate ester.

3. A composition according to claim 1 wherein the composition further comprises a suspending agent, and optionally one or more of a preservative, a buffer and an isotonizing agent.

4. A composition according to claim 3 wherein the suspending agent is sodium carboxymethyl cellulose and the surfactant is polysorbate 20.

5. A composition according to claim 4 wherein the preservative is benzyl alcohol and the isotonizing agent is mannitol or a phosphate buffer.

6. A composition according to claim 1 having a viscosity of less than 75 mPa.s.

7. A composition according to claim 1 comprising by weight based on the total volume of the composition:

(a) from 3 to 20% (w/v) of the prodrug;

(b) from 0.5 to 2% (w/v) of a wetting agent;

(c) one or more buffering agents sufficient to render the composition neutral to very slightly basic (up to pH 8.5);

(d) from 0.5 to 2% (w/v) of a suspending agent;

(e) up to 2% (w/v) preservatives; and

(f) water q.s. ad 100%.

8. A pharmaceutical composition as claimed in any one of claims 1 to 7 for use as a medicament in the treatment of psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioural disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioural disturbances in mental retardation and autism, Tourette'"'"'s syndrome, bipolar mania, depression, anxiety.

9. The use of a composition as claimed in any one of claims 1 to 7 for the preparation of a medicament for treating psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioural disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioural disturbances in mental retardation and autism, Tourette'"'"'s syndrome, bipolar mania, depression, anxiety.