Mapping Advantages and Challenges in Analytical Development for Fixed Dose Combination Products, a Review

Formulations containing more than one active ingredient are increasingly gaining popularity due to advantages with regard to patient convenience as well as reduced cost of production, packaging, and transportation. Such fixed-dose combinations (FDCs) demand for enhanced analytical methodologies and tools to efficiently achieve quality control of these complex products as compared to the conventional products containing only one active constituent. Highly efficient analytical methods can measure multiple constituents at once, improving their quality control. This review article discusses the challenges in the development of such methods due to the similarities or differences in the chemical identity of the participating drug molecules in an FDC. The latest developments in multiple analyte determination using various analytical techniques (HPLC, LC-MS, NMR, IR, powder XRD and DSC) are discussed, with a focus on special considerations in each case. The article discusses challenges with sample preparation of complex FDC products, and the use of Chemometrics and Quality by Design to develop efficient analytical methods. Lastly, an equation-based approach is proposed and demonstrated to arrive at a parameter referred to as "percentage efficiency gain" that would be useful in directly accessing the relevance and commercial benefits of a simultaneous method vis-a-vis separate methods for individual components.