Assessment of rate of drug release from oil vehicle using a rotating dialysis cell

The rate constants for transfer of model compounds (naproxen and lidocaine) from oily vehicle (Viscoleo(R)) to aqueous buffer phases were determined b y use of the rotating dialysis cell. Release studies were done for the part ly ionized compounds at several pH values. A correlation between the overal l first-order rate constant related to attainment of equilibrium, k(obs), a nd the pH-dependent distribution coefficient, D, determined between oil veh icle and aqueous buffer was established according to the equation: log k(ob s) = -0.71 log 0-0.22 (k(obs) in h(-1)). Based on this correlation it was s uggested that the rate constant of a weak electrolyte at a specified D valu e could be considered equal to the k(obs) value for a non-electrolyte posse ssing a partition coefficient, P-app, the magnitude of which was equal to D . Specific rate constants k(ow) and k(wo) were calculated from the overall rate constant and the pH-dependent distribution coefficient. The rate const ant representing the transport from oily vehicle to aqueous phase, k(ow), w as found to be significantly influenced by the magnitude of the partition c oefficient P-app according to: log k(ow)= -0.71 log P-app -log(P-app + 1)-0 .22 (k(ow) in h(-1)). (C) 2000 Elsevier Science B.V. All rights reserved.