Depot systems comprising cariprazine or salts thereof
Inventors
Rubnov, Shai • Marom, Ehud • GOPIN, Anna
Assignees
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Publication Number
US-12251380-B2
Publication Date
2025-03-18
Expiration Date
Abstract
The present invention provides long-acting parenteral pharmaceutical compositions including 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
The invention relates to a long-acting parenteral pharmaceutical composition provided as a solution that includes cariprazine or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable biodegradable carrier comprising poly(lactic-co-glycolic acid) (PLGA), and a biocompatible solvent. The composition is suitable for forming an in situ implant in a subject in need thereof following administration, and it releases a therapeutically effective amount of the cariprazine or salt for at least 4 weeks following a single administration.
The formulation uses a PLGA-based carrier combined with a biocompatible water-miscible solvent so that, upon contact with bodily fluids, a depot or in situ implant is formed. The long-acting release provides sustained release of cariprazine and metabolites desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR) for at least 4 weeks after a single dose.
The disclosed system is intended to provide prolonged therapeutic action compared with oral immediate release cariprazine hydrochloride, including pharmacokinetic assessment in a rat model following intramuscular injection. The described pharmacokinetic profile is reported as flattened plasma profiles and continuous release over at least one month.
Claims Coverage
The independent claim covers a long-acting parenteral solution composition that forms an in situ implant and provides cariprazine release for at least 4 weeks after a single administration. The independent claim contains multiple inventive features supported by dependent claims, including PLGA composition constraints, solvent selection, dissolution-based release performance constraints, and pharmacokinetic and administration-route constraints.
Long-acting in situ implant-forming parenteral solution
A long-acting parenteral pharmaceutical composition in the form of a solution comprising cariprazine or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable biodegradable carrier comprising poly(lactic-co-glycolic acid) (PLGA), and a biocompatible solvent, wherein the composition is suitable for forming an in situ implant in a subject in need thereof following administration, and wherein the composition releases a therapeutically effective amount of the cariprazine or a pharmaceutically acceptable salt thereof for at least 4 weeks following a single administration.
Dissolution-based release threshold performance
A composition providing specified cariprazine release limits in an aqueous medium containing 0.1% sodium lauryl sulfate when measured with dissolution apparatus type II, including less-than thresholds at 1–4 weeks and more-than 50% release at 5 weeks.
PLGA lactic-to-glycolic monomer molar ratio constraint
The PLGA contains a lactic-to-glycolic monomer molar ratio from 50:50 to 85:15.
Selected biocompatible solvent set
The biocompatible solvent is selected from benzyl alcohol, methyl benzoate, ethyl benzoate, n-propylbenzoate, isopropyl benzoate, butyl benzoate, isobutyl benzoate, tert-butyl benzoate, and benzyl benzoate.
Substantially constant plasma concentration window
The composition provides substantially constant cariprazine plasma concentrations between about 60 hours and about 600 hours after a single administration.
Intramuscular injection administration route
The method administers the long-acting parenteral pharmaceutical composition to the subject by intramuscular injection.
Overall, the claim set centers on an in situ implant-forming long-acting parenteral solution combining cariprazine or a pharmaceutically acceptable salt with a biodegradable PLGA carrier and a biocompatible solvent to achieve release for at least 4 weeks after a single administration. Dependent claim refinements emphasize PLGA monomer ratio, defined allowable solvents, dissolution test-based release constraints in 0.1% sodium lauryl sulfate with dissolution apparatus type II, and performance constraints such as substantially constant plasma concentrations and an intramuscular injection route.
Stated Advantages
Provides sustained release of a therapeutically effective amount of cariprazine or salt for at least 4 weeks following a single administration.
Reduces burst release as evaluated by dissolution testing in 0.1% sodium lauryl sulfate using dissolution apparatus type II.
Produces substantially constant cariprazine plasma concentrations over a defined window after a single administration.
Provides prolonged therapeutic action with flattened plasma profiles compared with oral immediate release cariprazine hydrochloride.
Documented Applications
Treatment of schizophrenia.
Treatment of major depressive disorder (MDD).
Treatment of bipolar disorder including manic or mixed episodes.
Treatment of bipolar depression.
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