Crystal Modification of Phenytoin with Polyethylene Glycol for Improving Mechanical Strength, Dissolution Rate and Bioavailability by a Spherical Crystallization Technique

Abstract

Phenytoin crystals with improved mechanical strength, dissolution rate and bioavailability were obtained by using a novel crystallization process termed “spherical crystallization.” An alkaline solution of phenytoin held at 40 °C was poured into a well dispersed mixture of isopropyl acetate and hydrochloric acid containing a water-soluble polymer, e.g. polyethylene glycol (PEG), at 20 °C. Fine crystals of phenytoin incorporating PEG in proportion to its concentration in the solvent were directly agglomerated. The agglomerates with PEG had a free-flowing property due to their spherical shape and smooth surface. The PEG incorporated in the agglomerate resulted in increased mechanical strength, dissolution rate and bioavailability of the resultant agglomerated crystals of phenytoin. © 1986, The Pharmaceutical Society of Japan. All rights reserved.