Improved kinetic parameter estimation in pH-profile data treatment

Statistical problems in temperature stability parameter estimation have bee n the subject of many papers whereas statistics in, pH-profile parameter es timation have focused little attention. However, the conventional two step method used in data treatment in both cases leads to identical statistical problems. The aim of this study is then to introduce a method that improves statistics in pH-profile parameter estimation. A one step non-linear metho d that takes into account the errors in drug content determination is propo sed. A mathematical relationship between drug content C, pH and time t is t ested. The proposed method allows the estimation of the specific kinetic co nstants and the dissociation constant (pK(a)) in a single run. The most lik ely experimental initial drug contents C-0j,. where j is the index of a giv en experiment, are also determined. This approach that takes into account a ll relevant experimental information for the estimation of kinetic paramete rs is more rigorous from a statistical viewpoint than the classical two ste p methods. Kinetic data from acetylsalicylic acid (ASA) hydrolysis was used for the tests. (C) 2000 Elsevier Science B.V. All rights reserved.