Pharmaceutical compositions comprising 4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-1-(4-fluorophenyl)butan-1-one for treating central nervous system disorders

Inventors

Li, Peng • Zhang, Qiang • Davis, Robert • Wennogle, Lawrence P.

Assignees

Intra Cellular Therapies Inc

Abstract

The invention relates to pharmaceutical compositions comprising compounds of Formula Q: wherein W is —N(CH3)—, and Y is —C(O)—, in free base or pharmaceutically acceptable salt form, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) pathway and/or the dopamine D2 receptor pathway, and methods of treating conditions of the central nervous system therewith.

Core Innovation

The invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable diluent or carrier in admixture with a compound of Formula Q and a polymeric matrix. The compound of Formula Q is provided in free base or pharmaceutically acceptable salt form, and the composition is a sustained-release injectable composition or a delayed-release injectable composition in a non-aqueous form where the pharmaceutically acceptable diluent or carrier is an organic solvent.

A central aspect is the use of a polymeric matrix in which the compound of Formula Q is dissolved or dispersed to enable sustained release or delayed release formulations. The document describes non-aqueous formulations using an organic solvent as the pharmaceutically acceptable diluent or carrier, including polymeric matrices suitable for extended pharmacokinetic profiles.

The document describes the clinical problem as the need for CNS disorder treatment strategies that address central nervous system disorders by improving pharmacokinetics through extended, sustained, or delayed release formulations. It further characterizes pharmacological pathway involvement including 5-HT2A receptor activity, serotonin transporter (SERT), and/or dopamine D2 receptor signaling, and describes therapeutic use in anxiety, depression, psychosis/schizophrenia, sleep disorders, migraine, and related CNS indications.

In addition, the document describes depot and prodrug formulation concepts in which prodrug forms can be cleaved to release an active compound. It also defines broad chemical coverage for substituted heterocycle fused gamma-carbolines through Formula I, Formula II, Formula III, and Formula IV, including pharmaceutically acceptable salt forms and selected diastereomeric purity ranges.

Claims Coverage

The partial claim set includes one independent claim. The independent claim covers a non-aqueous sustained-release or delayed-release injectable pharmaceutical composition comprising a compound of Formula Q and a polymeric matrix, with an organic-solvent carrier, and dependent claims narrow solvent properties, salt/free-base form, polymeric matrix configuration, and sustained-release duration windows.

Overall, the claim coverage is centered on non-aqueous sustained-release or delayed-release injectable pharmaceutical compositions using a compound of Formula Q dissolved or dispersed in a polymeric matrix with an organic-solvent carrier. Dependent features narrow the organic solvent to water-miscible solvents, specify Formula Q salt forms, define polymer and microspheric matrix configurations, add sustained-release duration windows, and include method coverage directed to inhibiting serotonin 5-hydroxytryptamine-2A receptor activity by administering the composition.

Stated Advantages

Documented Applications