Reaction #1483110

ord-362ac787d9b2419e8b184b5e68b65f9f

Reaction equation

C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](N)Cc2ccccc2)CSSC[C@@H](C(=O)N[C@H](CO)[C@@H](C)O)NC1=O.O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O
Octreotide pamoate
→
O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O
Pamoic Acid

Reactants

—
PLGA
C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](N)Cc2ccccc2)CSSC[C@@H](C(=O)N[C@H](CO)[C@@H](C)O)NC1=O.O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O
Octreotide pamoate

Reagents

None

Solvents

CCOC(C)=O
EtOAc
OCc1ccccc1
benzyl alcohol
—
in-water

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

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

Procedure

Microparticle formulations (Table 5, Q-W) were prepared by an oil-in-water emulsion/solvent extraction method. PLGA polymer (MW 24,000, 180 mg) was dissolved in EtOAc (1000 μL). Octreotide pamoate (20 or 40 mg) was dissolved in benzyl alcohol (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 in a ratio of 1:2 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.

Source

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