Analytical Method Selection for Drug Product Dissolution Testing

Abstract

Introduction Dissolution is a characterization test commonly used by the pharmaceutical industry to guide formulation design and control product quality. Often, it is a required performance test for solid dosage forms,transdermal patches,and suspensions. It is also the only test that measures the rate of in vitro drug release as a function of time, which can reflect either reproducibility of the product manufacturing process or, in limited cases, in vivo drug release. The objective of dissolution testing, in general,varies during the life cycle of a dosage form (1). The primary objective of dissolution testing at Phases 0 and I is to establish the dissolution mechanism. During Phases II and III, the objective shifts to developing an understanding of the impact of key formulation/process parameters on dissolution and an in vitro–in vivo correlation (IVIVC). At product registration and beyond,the goal is to identify a quality control (QC) dissolution test method to verify process and product consistency. The continual evolution of objectives during the drug product life cycle may require different detection methods in order to have effective and efficient dissolution tests. In general,analytical methods used for quantifying drug release in dissolution tests can be classified into four categories:spectrophotometric, chromatographic,mass spectrometric,and potentiometric. This article attempts to provide a comprehensive overview of these method categories, highlighting the advantages and limitations of each method as applied to dissolution testing. General considerations for method selection are discussed, focusing on five important analytical parameters: dynamic range,selectivity,extent of automation,efficiency,robustness,and compatibility with dissolution media. Finally,general guidance for method selection at different stages of drug product life cycle is presented.