Depot systems comprising Cariprazine or salts thereof
Inventors
Rubnov, Shai • Marom, Ehud • GOPIN, Anna
Assignees
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Publication Number
US-11931357-B2
Publication Date
2024-03-19
Expiration Date
Abstract
The present invention provides long-acting parenteral pharmaceutical compositions comprising a therapeutically effective amount of Cariprazine or salts thereof, in a depot form suitable for administering at a medically acceptable location in a subject in need thereof. The depot compositions are preferably in the form of in-situ implants suitable for subcutaneous or intramuscular administration and provide prolonged release of the Cariprazine active ingredient and/or its metabolites desmethyl Cariprazine (DCAR) and didesmethyl Cariprazine (DDCAR) for a period of at least 4 weeks following a single administration. The present invention further provides methods of use of the depot compositions for the treatment of schizophrenia, major depressive disorder, and bipolar disorder.
Core Innovation
A long-acting parenteral pharmaceutical composition is described for forming an in situ implant in a subject following administration. The composition includes a therapeutically effective amount of cariprazine or a pharmaceutically acceptable salt thereof, is in the form of a solution, and is configured to form the in situ implant and release the cariprazine or salt over an extended period.
The composition uses a pharmaceutically acceptable biodegradable carrier comprising poly(lactic-co-glycolic acid) (PLGA), with a molar ratio of lactic to glycolic monomers from 50:50 to 85:15 and an inherent viscosity range of about 0.1 to about 0.8 dl/g. The composition also includes a biocompatible solvent and is described to release the cariprazine or salt for at least 4 weeks following a single administration.
The formulation approach is presented in terms of long-acting continuous release and reduced release fluctuations relative to daily dosing, including reduced burst release and smoother plasma exposure for a period of at least 4 weeks. Therapeutic use is described for mental diseases or disorders, including schizophrenia, major depressive disorder, and bipolar disorder, with dosing described as a single administration of the long-acting parenteral composition.
Claims Coverage
The independent claim defines a long-acting parenteral, in-situ implant-forming solution using a specified PLGA carrier plus a biocompatible solvent, releasing cariprazine or a pharmaceutically acceptable salt for at least 4 weeks after a single administration. The claim set further includes refinements for solvents, excipients, dissolution and release testing, plasma concentration constraints, and therapeutic use for specific mental disorders.
Long-acting in situ implant-forming parenteral cariprazine solution
A long-acting parenteral pharmaceutical composition suitable for forming an in situ implant in a subject following administration, comprising a therapeutically effective amount of cariprazine or a pharmaceutically acceptable salt thereof, and being in the form of a solution, wherein the composition releases the cariprazine or a pharmaceutically acceptable salt thereof for at least 4 weeks following a single administration.
Biodegradable PLGA carrier defined by lactic:glycolic ratio and inherent viscosity
A pharmaceutically acceptable biodegradable carrier comprising poly(lactic-co-glycolic acid) (PLGA) containing a molar ratio of lactic to glycolic monomers of from 50:50 to 85:15 and having an inherent viscosity in the range of about 0.1 to about 0.8 dl/g.
Biocompatible solvent enabling the solution and in situ implant formation
The composition further comprises a biocompatible solvent, where the composition is configured as a solution and suitable for forming an in situ implant.
Selected biocompatible benzyl/benzoate-type solvent
A biocompatible solvent selected from benzyl alcohol or one of several benzyl/alkyl benzoates.
Optional pharmaceutically acceptable excipients including sustained release and pH adjusting agents
The composition further includes one or more pharmaceutically acceptable excipients selected from preservatives, sustained release agents, buffering agents, and pH adjusting agents, or combinations thereof.
Dissolution/release percentage constraints in aqueous medium
The composition provides specified cariprazine release levels in an aqueous medium containing 0.1% sodium lauryl sulfate when measured with a dissolution apparatus type II over multiple time points.
Therapeutically effective or substantially constant plasma concentration over time
The composition provides therapeutically effective cariprazine plasma concentrations for at least 4 weeks after a single administration, or maintains substantially constant cariprazine plasma concentrations between about 60 and 600 hours after a single administration.
Treatment of schizophrenia, major depressive disorder, or bipolar disorder
A method of treating a selected mental disease or disorder comprising administering the long-acting parenteral pharmaceutical composition to a subject, wherein the selected mental disease or disorder is schizophrenia, major depressive disorder, or bipolar disorder.
The claim coverage centers on a cariprazine or salt long-acting parenteral formulation that is an in-situ implant-forming solution. The inventive coverage is characterized by a biodegradable PLGA carrier with specified lactic:glycolic monomer ratio and inherent viscosity, combined with a biocompatible solvent, to achieve at least 4 weeks of release after a single administration, with further refinements including enumerated solvents, excipient categories, specified dissolution/release performance, plasma concentration constraints, and treatment of schizophrenia, major depressive disorder, and bipolar disorder.
Stated Advantages
Long-acting release for at least 4 weeks following a single administration.
Reduced burst release and smoother plasma exposure compared with daily oral dosing.
Documented Applications
Treating mental diseases or disorders in a subject by administering the long-acting parenteral pharmaceutical composition, including schizophrenia, major depressive disorder, and bipolar disorder (including manic or mixed episodes associated with bipolar I disorder and depressive episodes associated with bipolar I disorder).
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