Assessment of wettability and its relationship to the intrinsic dissolution rate of doped phenytoin crystals

It has been inferred previously that the changes in intrinsic dissolution rate (i.e.,.initial dissolution rate divided by the initial surface area; IDR) observed for phenytoin (5,5-diphenylhydantoin; DPH) crystals doped with traces of 3-acetoxymethyl-DPH (AMDPH), 3-propanoyloxymethyl-DPH (PMDPH) or 3-butanoyloxymethyl-DPH (BMDPH) are possibly linked to the following key factors: (a) crystal habit; (b) crystal imperfections; and (c) 'poisoning' of the active dissolution sites by the adsorbed dopants. To elucidate how these factors could have affected the observed IDR and to determine the relative contributions of these factors, the surface tensions of the pure and doped DPH crystals and of the three dopants were assessed using a previously established technique based on the change in sedimentation volume of particles in selected wetting liquid systems. In addition, the contact angles were measured for droplets of the wetting liquids on DPH compacts made from compressed DPH crystals (both pure and doped) and on dopant films formed from acetone solutions. With all the three dopants, a statistically significant positive correlation (r = 0.777; n = 12 (mean values); p < 0.05) existed between the surface tensions of the various DPH samples and the corresponding IDRs, suggesting that the observed increases in IDR may be attributable to the increases in wettability and vice versa. The estimated surface tensions of PMDPH (42.9 +/- 0.8 mN m(-1); n = 6) and AMDPH (44.1 +/- 1.1 mN m(-1); n = 7) were comparable to that of the pure recrystallized DPH sample (42.4 +/- 1.5 mN m(-1) n= 13) whereas m that of BMDPH (50.9 +/- 2.0 mN m(-1); n = 10) was significantly higher, reflecting similar wettabilities for the pure recrystallized DPH, AMDPH and PMDPH but significantly higher wettability for BMDPH. Complementary contact angle measurements also afforded values consistent with the observed wettabilities, i.e., high but similar contact angles for the pure DPH samples (theta(water)=65.8+/-1.1 degrees; n=20), AMDPH (theta(water)=68.5+/-0.8 degrees; n=52) and PMDPH (theta(water)=66.5+/-1.2 degrees; n=50); and low contact angle for BMDPH (theta(water)=45.0+/-1.7 degrees; n=66). Whilst the relatively good wettability of adsorbed BMDPH appears to be 'directly' responsible, at least in part, for the observed increases in IDR, the possibilities remain that the improved wettability of doped DPH crystals, particularly that observed with AMDPH as dopant, may be a result of a dopant-mediated augmentation of the density of structural defects at the crystal surface and/or of a habit-related increase in the areas of the relatively polar crystal faces.