Transmucosal methods for treating psychiatric and neurological conditions
Inventors
Li, Peng • Yao, Wei • Davis, Robert
Assignees
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Publication Number
US-12336989-B2
Publication Date
2025-06-24
Expiration Date
Abstract
The disclosure provides new transmucosal and subcutaneous pharmaceutical compositions comprising 1-(4-fluoro-phenyl)-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)-butan-1-one or 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d2-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one or comprising -(4-fluoro-phenyl)-4-((6bR,10aS)-1,1,2,2-d4-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one, in free base, co-crystal or salt form, together with methods of making and using them.
Core Innovation
The invention relates to transmucosal pharmaceutical formulations comprising 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d2-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one in tosylate salt form. The formulation is provided as a rapidly dissolving tablet or wafer, or as a sublingual tablet or wafer, and comprises from 0.01 to 30 mg of the Compound of Formula II, free base equivalent.
The invention further includes transmucosal formulations that comprise one or more fish gelatins in addition to the Compound of Formula II tosylate salt form. The formulations may include one or more excipients selected from cellulose, gelatin, sugar, carbohydrate, and polyol excipients, and are characterized by rapid mucosa absorption or dissolution, including dissolution or absorption in less than 30 seconds after administration.
The invention also provides prophylaxis or treatment methods for a disease or abnormal condition mediated by 5-HT2A receptor, serotonin transporter (SERT), and/or dopamine D1/D2 receptor signaling. The methods involve administering a therapeutically effective amount of the transmucosal formulation to a patient, with disease selection limited to enumerated psychiatric and neurological conditions, including sublingual administration in the method.
Claims Coverage
Three inventive features are identified across the independent claims, centered on the transmucosal formulation of Compound of Formula II, an added fish gelatin requirement in one claim, and a therapeutic use claim for receptor/transporter-mediated diseases.
Compound in tosylate salt form for transmucosal rapid dissolving tablet or wafer
A transmucosal pharmaceutical formulation comprising 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d2-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one in tosylate salt form, wherein the formulation is a rapidly dissolving tablet or wafer, or a sublingual tablet or wafer.
Dose range of Compound of Formula II (free base equivalent) in transmucosal formulation
The formulation comprises from 0.01 to 30 mg of the Compound of Formula II, free base equivalent.
Fish gelatin-containing transmucosal formulation with rapid dissolving or sublingual tablet or wafer
A transmucosal pharmaceutical formulation comprising 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d2-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one in tosylate salt form, wherein the formulation is a rapidly dissolving tablet or wafer, or a sublingual tablet or wafer, and wherein the formulation further comprises one or more fish gelatins.
Rapid mucosa absorption or dissolution in less than 30 seconds
The formulation is absorbed by the mucosa or dissolves in less than 30 seconds after administration.
The claim coverage centers on transmucosal formulations containing Compound of Formula II as a tosylate salt, provided in rapidly dissolving or sublingual tablet/wafer form with a specified 0.01–30 mg dose range. A further independent claim requires fish gelatins, and dependent claim language adds a mucosa absorption/dissolution performance constraint of less than 30 seconds. Related use claims apply the formulation to prophylaxis or treatment of receptor/transporter-mediated psychiatric and neurological diseases, including sublingual administration in the method context.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Prophylaxis or treatment of a disease or abnormal condition mediated by 5-HT2A receptor, serotonin transporter (SERT), and/or dopamine D1/D2 receptor signaling by administering a therapeutically effective amount of the transmucosal formulation to a patient.
Therapeutic use for diseases selected from depression, major depressive disorder (MDD), anxiety, psychosis, schizophrenia, obsessive-compulsive disorder, sexual disorders, migraine, attention deficit disorder, attention deficit hyperactivity disorder, sleep disorders, conditions associated with cephalic pain, social phobias, dementia, Alzheimer’s Disease, Parkinson’s dementia, and bipolar disorder.
Sublingual administration of a therapeutically effective amount of the transmucosal formulation for treating a selected disease or abnormal condition mediated by 5-HT2A receptor, SERT, and/or dopamine D1/D2 receptor signaling.
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