Modification of phenytoin crystals : influence of 3-propanoyloxymenthyl-5,5-diphenylhydantoin on solution-phase crystallization and related crystal properties

John David Gordon
Recent studies in our laboratory have demonstrated that doping of phenytoin (5,5-diphenylhydantoin; DPH) crystals with traces of 3-acetoxymethyl-5,5-diphenylhydantoin, AMDPH, during growth from methanol consistently modifies their physical properties e.g., habit, energy, surface area, dissolution rate (Chow and Hsia, 1991). AMDPH is a suggested ester prodrug of DPH (Varia et al., 1984). In addition to being structurally akin to DPH, AMDPH is not appreciably greater in molecular size than DPH,
more » ... ar size than DPH, which makes possible, from the thermodynamic standpoint, the incorporation of AMDPH into the crystal lattice of DPH. To investigate how the molecular sizes of the ester homologues of DPH influence their incorporation into DPH crystals and the resulting crystal properties, studies similar to those described above have been applied to another additive higher in the ester homologous series, viz. 3-propanoyloxymethyl-5,5-diphenylhydantoin (PMDPH) (Gordon and Chow, 1991). PMDPH , also cited as a prodrug candidate of DPH, differs from AMDPH in possessing an additional methylene group in its ester side chain (Varia et al., 1984). The effects of recrystallizing DPH from methanol under defined conditions in the presence of various concentrations of PMDPH were investigated. An increase in the concentrations of PMDPH (from 0.5 to 11 gL⁻¹) in the crystallization solutions at 30 °C brought about a linear increase in PMDPH sorption (0.03-0.57 mole %) by the DPH crystals, a morphological change of the crystal from needles to elongated plates, a drop in crystallization yield, a decrease in particle size and an increase in specific surface area of the crystals. Vigorous multiple washing of the doped crystals with methanol/water (5:95) detached ~ 70 ± 2 %w/w of PMDPH and a negligible amount of DPH (1.0 ± 0.1 %w/w), indicating that the additive was predominantly adsorbed on the crystal surface. While powder X-ray diffraction studies on the doped and pure crystals presented no significant differences in both their diffraction patterns and lat [...]
doi:10.14288/1.0098453 fatcat:s2jxhfbajjfdbej6smdiggrvc4