Acetonitrile → HCID 131732896, compound

HRID 2166985Notes

Reaction equation

HRID 2166985 reaction equation
[CH3:1][C@H:2]1[CH2:33][C:32]([CH3:34])=[CH:31][C@@H:30]([CH2:35][CH:36]=[CH2:37])[C:28](=[O:29])[CH2:27][C@H:26]([OH:38])[C@@H:25]([CH3:39])[C@@H:24](/[C:40](/[CH3:51])=[CH:41]/[C@H:42]2[CH2:47][C@@H:46]([O:48][CH3:49])[C@H:45]([OH:50])[CH2:44][CH2:43]2)[O:23][C:21](=[O:22])[C@H:20]2[N:15]([CH2:16][CH2:17][CH2:18][CH2:19]2)[C:13](=[O:14])[C:11](=[O:12])[C@:9]2([OH:52])[O:10][C@@H:5]([C@@H:6]([O:54][CH3:55])[CH2:7][C@H:8]2[CH3:53])[C@@H:4]([O:56][CH3:57])[CH2:3]1.[O:58]=[CH:59][C@@H:60]([C@H:62]([C@@H:64]([C@@H:66]([CH2:68][OH:69])[OH:67])[OH:65])[OH:63])[OH:61].C(#N)C>O>[CH3:1][C@H:2]1[CH2:33][C:32]([CH3:34])=[CH:31][C@@H:30]([CH2:35][CH:36]=[CH2:37])[C:28](=[O:29])[CH2:27][C@H:26]([OH:38])[C@@H:25]([CH3:39])[C@@H:24](/[C:40](/[CH3:51])=[CH:41]/[C@H:42]2[CH2:47][C@@H:46]([O:48][CH3:49])[C@H:45]([OH:50])[CH2:44][CH2:43]2)[O:23][C:21](=[O:22])[C@H:20]2[N:15]([CH2:16][CH2:17][CH2:18][CH2:19]2)[C:13](=[O:14])[C:11](=[O:12])[C@:9]2([OH:52])[O:10][C@@H:5]([C@@H:6]([O:54][CH3:55])[CH2:7][C@H:8]2[CH3:53])[C@@H:4]([O:56][CH3:57])[CH2:3]1.[O:58]=[CH:59][C@@H:60]([C@H:62]([C@@H:64]([C@@H:66]([CH2:68][OH:69])[OH:67])[OH:65])[OH:63])[OH:61]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal3×HCID 445643Tacrolimus3×

Product 1

HCID 131732896HCID 131732896, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-50 °C

Procedure

A formulation of tacrolimus (TAC) was produced using TAC and glucose (GLU) in ratio 1:1. The TAC:GLU 1:1 formulation was prepared using the ultra-rapid freezing (URF) process. The composition was prepared by dissolving TAC and GLU at a 1:1 ratio and 0.75% solids in a 60/40 mixture of acetonitrile and water. The solution of drug and excipient was applied to the surface of a solid substrate, which is cooled using a cryogenic substrate maintained at −50° C. The frozen compositions were then collected and the solvent was removed by lyophilization using a VirTis Advantage Lyophilizer (VirTis Company, Inc. Gardiner, N.Y.). The dried powders were stored at room temperature under vacuum. The result of XRD characterization (following the procedure in example 2) is that the formulation is amorphous. The result of SEM (following the procedure in example 4) is that the morphology is nanostructured aggregates with small primary particles consisting of TAC and GLU with primary particle sizes of about 100-300 nm.

Workup

  1. customThe composition was prepared
  2. temperatureis cooled
  3. customThe frozen compositions were then collected
  4. customthe solvent was removed by lyophilization
  5. customwere stored at room temperature under vacuum
  6. customThe result of XRD characterization (
  7. customThe result of SEM (

Sources & evidence

ORD record
ord-9286f1e0b8d6469f889b307efcc0fa1f
Source dataset
uspto-grants-2015_06
Patent number
US09044391B2

Reaction notes

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