Sustained-release pharmaceutical compositions comprising an antipsychotic drug and uses thereof
Inventors
Hong, Keelung • FANG, JONATHAN • Kao, Hao-Wen • Lin, Yi-Yu • GWATHNEY, Walter
Assignees
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Publication Number
US-12285524-B2
Publication Date
2025-04-29
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition comprising at least one liposome and an antipsychotic drug with a high drug to lipid ratio and encapsulation efficiency. The pharmaceutical composition improves the pharmacokinetic profile and sustains the release of the antipsychotic drug. Also provided is the method for treating schizophrenia or bipolar disorder using the pharmaceutical composition disclosed herein.
Core Innovation
The document describes sustained-release pharmaceutical compositions in which an antipsychotic drug is encapsulated in liposomes comprising a bilayer membrane. The bilayer membrane includes about 45 to about 79.9 mole % of a first lipid that is phosphatidylcholine (PC), HSPC, DSPC, DPPC, DMPC, PSPC, or combinations thereof, together with about 20 to about 55% mole % cholesterol and optionally 0.1-20% mole % of a second lipid such as phosphatidylethanolamine, phosphatidylglycerol, PEG-DSPE, DPPG, or combinations thereof. A trapping agent is also included as part of the liposome system.
The liposomes include a trapping agent selected among triethylammonium sucrose octasulfate, ammonium sulfate, dextran sulfate, or combinations thereof, with the trapping agent being matched to the specific antipsychotic drug. When the antipsychotic drug is aripiprazole or clozapine, the trapping agent is triethylammonium sucrose octasulfate. When the antipsychotic drug is olanzapine, the trapping agent is ammonium sulfate, while for quetiapine the trapping agent is dextran sulfate and for risperidone the trapping agent is triethylammonium sucrose octasulfate or ammonium sulfate.
The compositions are characterized by drug loading performance and encapsulation performance, including that the molar ratio of the drug to the lipid is equal to or higher than 0.47 and that the antipsychotic drug is encapsulated in the liposome with an encapsulation efficiency higher than 60%. The document reports in vitro release and in vivo pharmacokinetics, including prolonged half-life (t1/2) compared to free drug, and supports sustained release/extended half-life behavior for specific antipsychotics.
Claims Coverage
The independent claim defines a pharmaceutical composition with three main inventive elements: a specified liposome bilayer lipid composition, a trapping agent selected among specific options and matched to the antipsychotic drug, and performance constraints for drug-to-lipid molar ratio and encapsulation efficiency, together with coverage of multiple antipsychotic drugs.
Liposomal bilayer lipid composition
A liposome having a bilayer membrane comprising about 45 to about 79.9 mole % of a first lipid that is phosphatidylcholine (PC), HSPC, DSPC, DPPC, DMPC, PSPC, or any combination thereof; about 20 to about 55% mole % cholesterol; and optionally 0.1-20% mole % of a second lipid that is phosphatidylethanolamine, phosphatidylglycerol, PEG-DSPE, DPPG, or any combination thereof.
Drug-matched trapping agent selection
A trapping agent that is triethylammonium sucrose octasulfate, ammonium sulfate, dextran sulfate, or any combination thereof, wherein the trapping agent is triethylammonium sucrose octasulfate for aripiprazole or clozapine, ammonium sulfate for olanzapine, dextran sulfate for quetiapine, and triethylammonium sucrose octasulfate or ammonium sulfate for risperidone.
High drug-to-lipid ratio and high encapsulation efficiency
The molar ratio of the drug to the lipid is equal to or higher than 0.47 and the antipsychotic drug is encapsulated in the liposome with an encapsulation efficiency higher than 60%, wherein the antipsychotic drug is aripiprazole, olanzapine, quetiapine, risperidone, clozapine, or any combination thereof.
Across the independent claim, the coverage centers on liposome-encapsulated antipsychotic drugs using a defined bilayer lipid composition and an antipsychotic-specific trapping agent selection, while meeting performance thresholds for drug-to-lipid molar ratio (≥0.47) and encapsulation efficiency (>60%).
Stated Advantages
Improves pharmacokinetics by prolonging half-life compared to free antipsychotic drug.
Prolongs half-life and supports sustained release/extended half-life behavior.
Reduces dosing frequency.
Enables high drug-to-lipid ratio (≥0.47) and high encapsulation efficiency (>60%).
Documented Applications
Treatment and use of antipsychotic indications including schizophrenia and bipolar disorder using the sustained-release liposomal antipsychotic compositions.
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