Bioavailability study of a freeze-dried sodium phenytoin-milk formulation.
The problematic bioavailability of phenytoin's (5,5-diphenylhydantoin) oral formulations serves as a stimulus for examining new formulations and/or administration conditions that may provide more predictable absorption. Attempts to achieve more consistent peroral phenytoin bioavailability from conventional solid dosage forms include changes of binder and crystal size, use of salt form, and inclusion of the drug in cyclodextrins. In addition, various factors which may affect the environment and/or the physiology of the upper gastrointestinal tract can profoundly affect the absorption of phenytoin. Among other approaches, the use of drug-milk freeze-dried formulations has been proposed to overcome problems associated with dissolution-limited bioavailability. The effect has been attributed to the formation of an amorphous precipitate during the drying process which facilitates the re-dissolution of the drug during the regeneration of the milk solution. In this work, we report comparative bioavailability studies utilizing a freeze-dried sodium phenytoin-milk formulation and a capsule formulation administered with either water or milk. In addition, the interaction of the drug with milk components was evaluated in vitro through binding and solubility studies.
Macheras
P
P
Department of Pharmacy, University of Athens, Greece.
Ismailos
G
G
Reppas
C
C
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D005526:Food, Formulated; D005612:Freeze Drying; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008892:Milk / Q000378:metabolism*; D010672:Phenytoin / Q000378:metabolism / Q000493:pharmacokinetics*; D012995:Solubility; D013696:Temperature
D002214:Capsules; D010672:Phenytoin