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 inhibiting serotonin reuptake transporter activity
The invention relates to 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 in toluenesulfonic acid addition salt form: and methods of use in the treatment of diseases involving the 5-HT 2A receptor pathway, the serotonin transporter (SERT) pathway and/or the dopamine D 2 receptor pathway signaling systems.
1. A pharmaceutical composition comprising:
(i) a compound of Formula Q:
wherein:
X is —N(CH 3 )—; and
Y is —C(═O)—;
in toluenesulfonic acid addition salt form; and
(ii) a polymeric matrix.
2. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable diluent or carrier.
3. The pharmaceutical composition according to claim 1 , wherein:
(a) the compound of Formula Q in toluenesulfonic acid addition salt form is either dissolved or dispersed in the polymeric matrix; and
(b) the pharmaceutical composition further comprises a pharmaceutically acceptable diluent or carrier.
4. The pharmaceutical composition according to claim 3 , wherein the pharmaceutical composition is formulated as an injectable composition for sustained-release and/or delayed-release of the compound of Formula Q in toluenesulfonic acid addition salt form.
5. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is formulated for controlled-release and/or sustained-release of the compound of Formula Q in toluenesulfonic acid addition salt form over a period of 7 days, 14 days, 30 days, 60 days or 90 days.
6. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition further comprises a vehicle comprising a viscosity enhancing agent.
7. The pharmaceutical composition according to claim 6 , wherein the viscosity enhancing agent is sodium carboxymethylcellulose.
8. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises one or more polymers selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(citric acid), poly(malic acid), poly(beta-hydroxybutyric acid), lactic acid-glycolic acid copolymer, poly(lactide-co-glycolide), 2-hydroxybutyric acid-glycolic acid copolymer, poly(lactic acid)-poly(ethylene glycol) copolymer, poly(glycolic acid)-poly(ethylene glycol) copolymer, a poly(alkyl alpha-cyanoacrylate), a poly(alkylene oxalate), a poly(orthoester), a polycarbonate, a poly(orthocarbonate), a polyamino acid, a hyaluronic acid ester, a poly(aliphatic carboxylic acid), a copolyoxalate, a polycaprolactone, a polydioxonone, a poly(acetal), a poly(lactic acid-caprolactone) and a poly(glycolic acid-caprolactone).
9. The pharmaceutical composition according to claim 8 , wherein the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer.
10. The pharmaceutical composition according to claim 9 , wherein the polymeric matrix is a microsphere comprising a biodegradable poly(D,L-lactide-co-glycolide) polymer.
11. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix is a biodegradable poly(D,L-lactide-co-glycolide) microsphere.
12. A pharmaceutical composition or device comprising:
(a) a gelatin capsule containing the pharmaceutical composition according to claim 1 ;
(b) a multilayer wall superposed on the gelatin capsule comprising in outward order from the capsule:
(i) a barrier layer;
(ii) an expandable layer; and
(iii) a semipermeable layer; and
(c) an orifice formed or formable through the wall.
13. A pharmaceutical composition or device comprising:
(a) a first layer containing the pharmaceutical composition according to claim 1 ;
(b) a second layer containing a polymer;
(c) an outer wall surrounding the first layer and the second layer; and
(d) an orifice in the outer wall.
14. A method for inhibiting serotonin reuptake transporter activity in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 1 .
15. The method according to claim 14 , wherein the patient has a disorder involving the serotonin (5-hydroxytryptamine) 2A pathway, the dopamine D2 receptor pathway and/or the serotonin reuptake transporter pathway.
16. The method according to claim 15 , wherein the disorder is selected from a group consisting of (1) psychosis in a patient suffering from depression, (2) depression in a patient suffering from psychosis, (3) a mood disorder associated with psychosis, and (4) a sleep disorder associated with psychosis.
17. The method according to claim 14 , wherein the patient has a disorder selected from a group consisting of obesity, anxiety, depression, psychosis, schizophrenia, migraine, a sleep disorder, a sexual disorder, a gastrointestinal disorder, a condition associated with cephalic pain, a social phobia, an agitation in dementia, an agitation in autism and an agitation in a related autistic disorder.
18. The method according to claim 17 , wherein the disorder is depression.
19. The method according to claim 17 , wherein the disorder is psychosis.
20. The method according to claim 17 , wherein the disorder is schizophrenia.