Reaction #1269837

ord-2178096666c84924908923167b0ca2c0

Reaction equation

FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br
Perfluorooctyl bromide
NC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H](N)C[C@@H]2N)[C@H](N)C[C@@H]1O.O=S(=O)(O)O
Tobramycin sulfate
CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(=O)([O-])OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC
DSPC
O.O.[Ca+2].[Cl-].[Cl-]
calcium chloride dihydrate
→
NC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H](N)C[C@@H]2N)[C@H](N)C[C@@H]1O
Tobramycin

Reactants

FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)Br
Perfluorooctyl bromide
NC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H](N)C[C@@H]2N)[C@H](N)C[C@@H]1O.O=S(=O)(O)O
Tobramycin sulfate
CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(=O)([O-])OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC
DSPC
O.O.[Ca+2].[Cl-].[Cl-]
calcium chloride dihydrate
—
phosphatidylcholine
—
PFOB-in-water

Reagents

None

Solvents

O
water
O
Water

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    DryingA tobramycin sulfate dry powder composition
  2. 2
    Otheris prepared
  3. 3
    workup.ADDITIONThe resulting lipid dispersion is mixed in an UltraTurrax T-50 (IKA Labortechnik) at 8,000 rpm for 5 min
  4. 4
    workup.ADDITIONunder mixing
  5. 5
    workup.ADDITIONAfter the addition
  6. 6
    workup.ADDITIONis mixed for an additional 10 min at 10,000 rpm
  7. 7
    OtherEmulsification in the UltraTurrax produces droplets in the micron-size range
  8. 8
    Otherdrying
  9. 9
    OtherThe feedstock is then spray dried
  10. 10
    Otherto obtain a dry powder formulation

Procedure

A tobramycin sulfate dry powder composition is prepared according to the following procedure. Sterile Water for Irrigation (SWFI) is heated above the gel to liquid crystal temperature (about 80° C.) of disteroyl phosphatidylcholine (DSPC). DSPC and calcium chloride dihydrate are then added to the heated water. The resulting lipid dispersion is mixed in an UltraTurrax T-50 (IKA Labortechnik) at 8,000 rpm for 5 min. Perfluorooctyl bromide (PFOB) is then added dropwise (15 ml/min) to the lipid dispersion under mixing. After the addition is complete the resulting PFOB-in-water emulsion is mixed for an additional 10 min at 10,000 rpm. Emulsification in the UltraTurrax produces droplets in the micron-size range. Tobramycin sulfate is then dissolved in the continuous phase of the emulsion and the resulting dispersion is used as the feedstock for spray drying. The feedstock is then spray dried to obtain a dry powder formulation having the composition set forth in Table 1 below.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08664187B2uspto-grants-2014_03