Bioavailability of phenytoin sodium capsules available in Thailand part I : In vitro study

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 specification. This result revealed that phenytoin capsules available in Thailand did not have homogeneous 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.