Mooney K G, Rodriguez-Gaxiola M, Mintun M, Himmelstein K J, Stella V J
J Pharm Sci. 1981 Dec;70(12):1358-65. doi: 10.1002/jps.2600701218.
This study investigated the possible effects of simultaneous, noninstantaneous, reversible chemical ionization of carbon acids on the dissolution of a typical pharmaceutical carbon acid, phenylbutazone, and its deutero analog. The dissolution rate versus pH profile for phenylbutazone was consistent with phenylbutazone acting as if it were an acid where the ionization can be considered instantaneous. In view of the dissolution behavior of phenylbutazone under various conditions, it is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization. Slowing the reaction time with a primary isotope effect by deuterium substitution for the ionizable proton caused significant deviation from classical behavior for d-phenylbutazone.
本研究调查了碳酸的同步、非瞬时、可逆化学电离对典型药用碳酸——保泰松及其氘代类似物溶解的可能影响。保泰松的溶解速率与pH关系曲线表明，保泰松的行为类似于一种酸，其电离可视为瞬时的。鉴于保泰松在各种条件下的溶解行为，该化合物所表现出的非瞬时电离动力学不太可能在体外或体内决定溶解速率方面起主要作用，因为保泰松溶解时在典型水扩散层中的平均停留时间长于其电离反应时间。用氘取代可电离质子通过一级同位素效应减慢反应时间，导致d - 保泰松的行为显著偏离经典行为。
