01 May 2019

USP 4 – From Discovery Phase to Preclinical Development.

The flow-through cell dissolution method (USP <711>, Apparatus 4 / Ph. Eur. 2.9.3, Apparatus 4) is a well-known approach for low-solubility BCS Class II and IV active pharmaceutical ingredients (APIs) and their drug products.

Flow-through cell dissolution is suitable for evaluating and comparing APIs and formulations and for exploring special issues related to new chemical entities. The flow-through dissolution equipment (FTDE) is used mainly for research and development studies, but pharmacopeias also make it possible to develop a method for routine analysis on FTDE, and researchers can achieve significant results even when only a few milligrams of a new chemical entity is available. Furthermore, the volume of dissolution medium required is at least four times less, which is an economic advantage.

Predicting how a drug will behave in humans before clinical testing requires a battery of sophisticated in vitro tests that complement traditional in vivo animal safety assessments. The quantities of promising new candidates available for early pharmaceutical evaluation are usually limited to between 10 and 20 mg during the lead optimization process. To choose the best compounds from a biopharmaceutical point of view, physicochemical parameters such as solubility, dissolution rate, hygroscopicity, lipophilicity, pKa, stability, polymorphism, and particle characteristics must be evaluated as early as possible and, above all, with the highest accuracy.

Read the complete article by Márta Venczel, Tamás Sovány, Klára Pintye-Hódi, and Gabriella Ujhelyi at www.dissolutiontech.com