EP-4736842-A1 - IN SITU GEL FORMULATION AND PREPARATION METHOD THEREOF

Abstract

In some embodiments of the present disclosure, an in situ gel formulation is provided, comprising an active ingredient, solvent, polymer and lipid, in which the polymer comprises polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), or a combination thereof, and the lipid comprises fatty acid, fatty alcohol, glyceride, phospholipid, or a combination thereof. In some embodiments of the present disclosure, a preparation method of an in situ gel formulation is further provided.

Inventors

• LEE, Hsiang-Ju
• SU, CHIA-YU
• CHEN, MEI-HUEI
• LIU, YI-HSIANG
• JHAN, HUA-JING
• JIAN, CHI-HENG

Assignees

• ANXO Pharmaceutical Co., Ltd.

Dates

Publication Date

20260506

Application Date

20251103

Claims (15)

1. An in situ gel formulation, characterized by comprising: an active ingredient; a solvent; polymer, wherein the polymer comprises polylactic-co-glycolic acid, polylactic acid, or a combination thereof; and lipid, wherein the lipid comprises fatty acid, fatty alcohol, glyceride, phospholipid, or a combination thereof.
2. The in situ gel formulation of claim 1, characterized in that a weight percentage of the active ingredient is from 0.1% to 35% based on 100% by weight percentage of the in situ gel formulation.
3. The in situ gel formulation of any one of claims 1 to 2, characterized in that the active ingredient comprises a psychiatric drug or an antidiabetic drug.
4. The in situ gel formulation of claim 3, characterized in that the psychiatric drug comprises cariprazine, brexpiprazole, paliperidone, risperidone, aripiprazole, lurasidone, or a pharmaceutically acceptable salt of any of the foregoing psychiatric drug, or a combination thereof, wherein the antidiabetic drug comprises empagliflozin, dapagliflozin, canagliflozin, semaglutide, liraglutide, dulaglutide, tirzepatid, a pharmaceutically acceptable salt of any of the foregoing antidiabetic drug, or a combination thereof.
5. The in situ gel formulation of any one of claims 1 to 4, characterized in that a weight percentage of the polymer is from 2.5% to 20% based on 100% by weight percentage of the in situ gel formulation.
6. The in situ gel formulation of any one of claims 1 to 5, characterized in that a molar ratio of lactic acid to glycolic acid in the polylactic-co-glycolic acid is from 50:50 to 99:1.
7. The in situ gel formulation of any one of claims 1 to 6, characterized in that a weight percentage of the lipid is from 17.5% to 60% based on 100% by weight percentage of the in situ gel formulation.
8. The in situ gel formulation of any one of claims 1 to 7, characterized in that a weight percentage of the lipid is from 55% to 95% based on 100% by total weight percentage of the polymer and the lipid.
9. The in situ gel formulation of any one of claims 1 to 8, characterized in that a weight percentage of the polymer and the lipid is from 25% to 65% based on 100% by weight percentage of the in situ gel formulation.
10. The in situ gel formulation of any one of claims 1 to 9, characterized in that the in situ gel formulation further comprises a surfactant having a hydrophilic-lipophilic balance value ranging from 15 to 20, and a weight percentage of the surfactant is from 2.5% to 10% based on 100% by weight percentage of the in situ gel formulation.
11. A preparation method of an in situ gel formulation, characterized by comprising: mixing an active ingredient, polymer and a first solvent to form a first mixture; mixing lipid and a second solvent to form a second mixture; and mixing the first mixture and the second mixture to form an in situ gel formulation.
12. The preparation method of claim 11, characterized in that the mixing the active ingredient, the polymer and the first solvent comprises: mixing the active ingredient and the first solvent to form a pre-mixture; and mixing the pre-mixture and the polymer to form the first mixture.
13. The preparation method of any one of claims 11 to 12, characterized in that the mixing the lipid and the second solvent comprises mixing the lipid, the second solvent and a surfactant.
14. A preparation method of an in situ gel formulation, characterized by comprising: mixing polymer and a solvent to form a polymer mixture; mixing an active ingredient and lipid to form a lipid mixture; and mixing the polymer mixture and the lipid mixture to form an in situ gel formulation.
15. The preparation method of claim 14, characterized in that the mixing the polymer and the solvent comprises mixing the polymer, the solvent and a surfactant.

Description

BACKGROUND Field of Invention The present disclosure relates to in situ gel formulation and preparation method thereof. In particular, the present disclosure relates to in situ gel formulation comprising polymer and lipid. Description of Related Art The in situ gel formulation is a gel implant formulation with sustained-release properties and usually required for high content of polymer. However, high content of polymer has certain drawbacks such as, the use of larger needle sizes due to excessively high viscosity, storage and transportation costs due to requirement for low storage temperature to maintain quality, inflammatory reactions caused by polymer degradation by-products. Therefore, how to provide an in situ gel formulation to improve the above mentioned problem remains to be solved. SUMMARY In one aspect of the present disclosure, an in situ gel formulation is provided, comprising an active ingredient, solvent, polymer and lipid, in which the polymer comprises PLGA, PLA, or a combination thereof, and the lipid comprises fatty acid, fatty alcohol, glyceride, phospholipid, or a combination thereof. In some embodiments, a weight percentage of the active ingredient is from 0.1% to 35% based on 100% by weight percentage of the in situ gel formulation. In some embodiments, the active ingredient comprises a psychiatric drug, or an antidiabetic drug. In some embodiments, the psychiatric drug comprises cariprazine, brexpiprazole, paliperidone, risperidone, aripiprazole, lurasidone, or a pharmaceutically acceptable salt of any of the foregoing psychiatric drug, or a combination thereof. In some embodiments, the antidiabetic drug comprises empagliflozin, dapagliflozin, canagliflozin, semaglutide, liraglutide, dulaglutide, tirzepatid, a pharmaceutically acceptable salt of any of the foregoing antidiabetic drug, or a combination thereof. In some embodiments, a weight percentage of the polymer is from 2.5% to 20% based on 100% by weight percentage of the in situ gel formulation. In some embodiments, a molar ratio of lactic acid to glycolic acid in the polylactic-co-glycolic acid (PLGA) is from 50:50 to 99:1. In some embodiments, a weight percentage of the lipid is from 17.5% to 60% based on 100% by weight percentage of the in situ gel formulation. In some embodiments, a weight percentage of the lipid is from 55% to 95% based on 100% by total weight percentage of the polymer and the lipid. In some embodiments, a weight percentage of the polymer and the lipid is from 25% to 65% based on 100% by weight percentage of the in situ gel formulation. In some embodiments, the solvent includes ethanol (EtOH), dimethyl sulfoxide (DMSO), 1-methyl-2-pyrrolidone (NMP), or a combination thereof. In some embodiments, the in situ gel formulation further comprises a surfactant. In some embodiments, the surfactant has a hydrophilic-lipophilic balance (HLB) value ranging from 15 to 20. In some embodiments, a hydrophilic-lipophilic balance (HLB) value of the surfactant is from 16 to 18. In some embodiments, a weight percentage of the surfactant is from 2.5% to 10% based on 100% by weight percentage of the in situ gel formulation. In one aspect of the present disclosure, a preparation method of an in situ gel formulation is provided, comprising: mixing an active ingredient, polymer and a first solvent to form a first mixture; mixing lipid and a second solvent to form a second mixture; and mixing the first mixture and the second mixture to form an in situ gel formulation. In some embodiments, the mixing the active ingredient, the polymer and the first solvent comprises: mixing the active ingredient and the first solvent to form a pre-mixture; and mixing the pre-mixture and the polymer to form the first mixture. In some embodiments, the mixing the lipid and the second solvent comprises mixing the lipid, the second solvent and a surfactant. In one aspect of the present disclosure, a preparation method of an in situ gel formulation is provided, comprising: mixing polymer and a solvent to form a polymer mixture; mixing an active ingredient and lipid to form a lipid mixture; and mixing the polymer mixture and the lipid mixture to form an in situ gel formulation. In some embodiments, the mixing the polymer and the solvent comprises mixing the polymer, the solvent and a surfactant. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1A illustrates a flow chart of a preparation method of an in situ gel formulation in some embodiments of the present disclosure.Fig. 1B illustrates a flow chart of another preparation method of an in situ gel formulation in some embodiments of the present disclosure.Fig. 2 illustrates the release profiles of part (2) of Example 1 (active ingredient: brexpiprazole; the control group: BA12FD) in the in vitro release test.Fig. 3 illustrates the release profiles of part (2) of Example 2 (active ingredient: cariprazine; the control groups: TF20-752 and TF20-502) in the in vitro release test.Fig. 4 illustrates the release profiles of