Bioavailability of Phenytoin Sodium Capsules Available in Thailand Part I : In vitro Study
CHUTHAMANEE SUTHISISANG, Ph.D.*, NALIN PAYAKACHAT, M.Sc.**
Affiliation : * Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, ** Department of Pharmacology, Faculty of Pharmaceutical Science, Silapakorn University, Nakornpathom 73000. Thailand.
Abstract
Phenytoin is commonly used as an antiepileptic drug worldwide. The unique properties
of phenytoin such as poor water solubility and zero-order kinetics of its metabolism, together
with difference in pharmaceutical formulations can result in dramatic changes in bioavailability
of phenytoin capsule.
The innovator (Dilantin® , Parke Davis), three local brands (brand A, B and C) were
investigated for pharmaceutical characteristics including drug content, content uniformity, and
dissolution. All these tests were performed as described in the monograph of extended phenytoin
sodium capsules in USP XXII with slight modification in HPLC analysis. It was found that all
the products, except brand C, had drug content and content uniformity within the standard range.
Brand A and brand C failed to meet the USP XXII specification for the dissolution test. Per cent
dissolution of brand A was lower whereas per cent dissolution of brand C was much higher than
the standard value. The qualities of innovator and brand B were within the pharmacopoeial specifi-
cation.
This result revealed that phenytoin capsules available in Thailand did not have homo-
geneous pharmaceutical equivalence which may lead to difference in plasma phenytoin levels (see
part II : In vivo study). Thus, changing the brand of phenytoin in stable epileptic patients should
be performed with caution.
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