Larsen D H, Fredholt K, Larsen C
Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Eur J Pharm Sci. 2000 Sep;11(3):223-9. doi: 10.1016/s0928-0987(00)00105-6.
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)).
使用旋转透析池测定了模型化合物（萘普生和利多卡因）从油性载体（Viscoleo）转移至水性缓冲相的速率常数。对部分离子化的化合物在几个pH值下进行了释放研究。根据以下方程建立了与达到平衡相关的总一级速率常数k(obs)与在油性载体和水性缓冲液之间测定的pH依赖性分配系数D之间的相关性：logk(obs)= -0.71 logD - 0.22（k(obs)单位为h(-1)）。基于这种相关性，有人提出，在特定D值下，弱电解质的速率常数可被视为与具有分配系数P(app)且大小等于D的非电解质的k(obs)值相等。从总速率常数和pH依赖性分配系数计算出特定的速率常数k(ow)和k(wo)。发现代表从油性载体向水相传输的速率常数k(ow)受分配系数P(app)大小的显著影响，关系如下：logk(ow)= -0.71 logP(app) - log(P(app) + 1) - 0.22（k(ow)单位为h(-1)）。
