Phenytoin soluble salt

Phenytoin is an anticonvulsant widely used in the treatment of epilepsy The properties of phenytoin resemble those of barbiturates. It is a cyclic imide with a pKa of 8.3. The anion is stabilised by resonance of the negative charge onto the oxygens of the carbonyl group and the drug is usually administered as the sodium salt to increase water solubility See Figure 3.15. 

FIGURE 41.13 Phosphate esters of cUn-damycin and of 3-hydroxymethyl-phenytoin (as sodium salts) are freely soluble in water and allow painless injections. 

Diphenylhydantoin sodium salt 2, 4-Imidazolidinedione, 5, 5-diphenyl-monosodium salt Diphenylhydantoin Sodium Diphenin Soluble Phenytoin U.S.P., B.P, Eur. P, Ind. P. Diphentoin (Beeeham) Epanutin Infatabs (Parke-Davis, U.K.) ... 

Phenytoin is the prototype and most commonly prescribed member of the hydantoin family of drugs. Bioequivalency is a problem with the hydantoins because of their very poor water solubility ( 32 mg/L) and a low therapeutic ratio. Phenytoin exhibits nonlinear pharmacokinetics that exaggerate the effects of changes in the fraction of dose absorbed. Its apparent pKa is in the range of 8.06 to 8.33 and, thus, can form a water-soluble sodium salt ( 15 mg/mL at solution pH >11). ... 

Note. Phenytoin being poorly water-soluble is mostly used as its sodium salt by enolization of the imidazoline ring and subsequent treatment with a calculated quantum of NaOH to obtain Phenytoin Sodium. 

Biological factors may change the solubility or dissolution rate of the active substance from the medicinal product as well. The residence time in the stomach may increase the dissolution of poorly water-soluble active substances and change their bioavailabiUty. The pH in the stomach or the intestine may influence dissolutirm rates of acidic or basic active substances whose solubDity is pH-dependent. Bile salts may increase the dissolution rate and thereby the absorption of poorly water-soluble active substances such as ciclospoiine, phenytoin, levothyroxine and tacrolimus. Though, it has been shown that the association with bile acids reduces the absorption of the hydrophiUc beta-blocker atenolol. 

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