Sorbitol → 5,5-Diphenylhydantoin

HRID 1872473Notes

Reaction equation

HRID 1872473 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[NH:13][C:11](=[O:12])[N-:10][C:8]2=[O:9])=[CH:3][CH:2]=1.[Na+].OC[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.NC(CO)(CO)CO>C(O)C>[CH:17]1[CH:18]=[CH:19][C:14]([C:7]2([C:4]3[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=3)[NH:13][C:11]([OH:12])=[N:10][C:8]2=[O:9])=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 5780SorbitolHCID 6503Tris(hydroxymethyl)aminomethane2×HCID 657302Diphenylhydantoin sodium2×

Product 1

HCID 17755,5-Diphenylhydantoin

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A drug phenytoin composition is prepared as follows: first, 2,580 g of polyethylene oxide having a weight-average molecular weight of 200,000 is passed through a 40-mesh screen. Then, 1,290 g of the screened polyethylene oxide is placed into the bowl of a mixer. Then, 2,400 g of sodium phenytoin is placed in the bowl over the polyethylene oxide. Next, 300 g of polyvinylpyrrolidone of 40,000 viscosity-average molecular weight is passed through a 40-mesh screen and added to the mixer. The remaining 1,290 g of polyethylene oxide is then added to the bowl. Next, 300 g of sorbitol and 360 g of tromethamine USP (2-amino-2-hydroxymethyl-1,3-propanediol) is passed through a 40-mesh screen and added to the mixer. The addition of the dry ingredients into the bowl is performed with the sodium phenytoin located between the two layers of polyethylene oxide. The ingredients are mixed for 5 minutes to produce a homogenous blend. The granulation process is initiated by the gradual addition of 3,200 g of ethyl alcohol to the mixer with continuous mixing. Mixing is continued over a period of 5 to 10 minutes to effect a consistency to change the dry powder to granules. The wet granulation is dried at 40° C. for 16 hours and then passed through a fluid air mill with a 7-mesh screen for size reduction. Next, the size reduced granules are placed into a blender. Then, 60 g of magnesium stearate that has been passed through a 60-mesh screen is added to the granulation, and all the ingredients mixed for a minute. This preparation provides a phenytoin composition comprising sodium phenytoin, polyethylene oxide, polyvinylpyrrolidone, tromethamine, sorbitol and magnesium stearate, useful for the therapeutic management of epilepsies.

Workup

  1. customA drug phenytoin composition is prepared
  2. additionadded to the mixer
  3. additionadded to the mixer
  4. additionThe addition of the dry ingredients into the bowl
  5. additionThe ingredients are mixed for 5 minutes
  6. customto produce a homogenous blend
  7. additionMixing
  8. customThe wet granulation is dried at 40° C. for 16 hours
  9. additionis added to the granulation, and all the ingredients
  10. additionmixed for a minute

Sources & evidence

ORD record
ord-efeeae377ae7403fa75711f7b5a9d799
Source dataset
uspto-grants-2000_08
Patent number
US06110499

Reaction notes

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