难溶性药物溶出度方法开发DT200402 A02.pdfVIP

Developing a Discriminating Dissolution Procedure for a Dual Active Pharmaceutical Product with Unique Solubility Characteristics Lagace, M.1,2, Gravelle, L. 2, Di Maso, M. 2 and McClintock, S.2 e-mail: marylene_lagace@ Abstract Regulatory agencies often consider USP dissolution methods developed using the slowest paddle speed (50 rpm) to repre- sent the most appropriate operating condition since they tend to produce the steepest drug release profiles. A steep drug release profile is frequently assumed to provide optimum discriminating power either to distinguish small variations in the tablet manufacturing process or to detect stability changes on storage. However,for certain tablet formulations it has been demonstrated that drug release profiles generated at 50 rpm can in fact be a reflection of system artifacts rather than a discriminatory tool. Higher paddle speeds which result in flatter drug release profiles can,in some cases,more accurately reflect true formulation changes. This point is highlighted in the description of the development of a dissolution method for a compressed tablet containing two active pharmaceutical ingredients (API). The selection of dissolution medium for a tablet with two APIs having very different solubility properties is detailed. The effects of paddle speed on system performance and method discriminating power are critically evaluated. Introduction To ensure good mixing of the drug and excipients in issolution testing is a required test currently used to the dissolution vessel, a suitable apparatus and rotational demonstrate the performance of all solid oral dosage speed should be selected. The basket method (Apparatus Dforms in which absorption of the drug is necessary 1) is routinely used for capsule formulations at agitation for the