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) to aqueous buffer phases were determined by use of the rotating dialysis cell. Release studies were done for the partly ionized compounds at several pH values. A correlation between the overall first-order rate constant related to attainment of equilibrium, k(obs), and the pH-dependent distribution coefficient, D, determined between oil vehicle and aqueous buffer was established according to the equation: logk(obs)=-0.71 logD-0.22 (k(obs) in h(-1)). Based on this correlation it was suggested that the rate constant of a weak electrolyte at a specified D value could be considered equal to the k(obs) value for a non-electrolyte possessing 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 constant representing the transport from oily vehicle to aqueous phase, k(ow), was found to be significantly influenced by the magnitude of the partition coefficient P(app) according to: logk(ow)=-0.71 logP(app)-log(P(app)+1)-0.22 (k(ow) in h(-1)).
Larsen
D H
DH
Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Fredholt
K
K
Larsen
C
C
D000074263:Coconut Oil; D003059:Cocos; D003692:Delayed-Action Preparations; D003956:Dialysis / Q000379:methods; D004337:Drug Carriers; D007700:Kinetics; D008012:Lidocaine / Q000737:chemistry* / Q000493:pharmacokinetics; D008954:Models, Biological; D009288:Naproxen / Q000737:chemistry* / Q000493:pharmacokinetics; D010938:Plant Oils
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010938:Plant Oils; D009288:Naproxen; D008012:Lidocaine; D000074263:Coconut Oil