Reaction #1483113

ord-24bf91850e6548a7ade645c227b81ec0

Reaction equation

CC(=O)O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1

Leuprolide acetate

→

CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1

Leuprolide

Yield 70.0%

Reactants

—

PLGA

Leuprolide acetate

Reagents

None

Solvents

CH2Cl2

BnOH

Conditions

Detailed conditions

See reaction.notes.procedure_details.

Workup

1
workup.ADDITIONadded to the polymer solution
2
Otheryielding a homogeneous organic phase
3
Otherto provide an emulsion
4
OtherThe emulsion was collected directly into a 0.3% PVA solvent extraction solution (150 mL)
5
Extractionto extract EtOAc
6
FiltrationHardened microparticles were collected by filtration
7
Washwashed with water, air
8
Otherdried
9
Otherstored at 4° C

Procedure

PLGA polymer (MW 24,000, 160 mg) was dissolved in CH2Cl2 (1000 μL). Leuprolide acetate (40 mg) was dissolved in BnOH (1000 μL) and added to the polymer solution yielding a homogeneous organic phase. The resulting organic phase was combined with a 1% PVA aqueous phase to provide an emulsion. The emulsion was collected directly into a 0.3% PVA solvent extraction solution (150 mL) and stirred for four hours to extract EtOAc. Hardened microparticles were collected by filtration, washed with water, air dried and stored at 4° C. This provided formulation BI (140 mg, 70.0% yield) with a median particle size 50.1 μm. The core load (1.99%), encapsulation efficiency (9.95%) and in vitro burst (1.63%) were determined by RP-HPLC assay.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08900636B2uspto-grants-2014_12