Rationale and strategies for formulation development of oral fixed dose combination drug products

The use of fixed dose combination (FDC) drug therapies has been world-widely accepted for long years due to providing better disease treatment with enhanced therapeutic efficacy and safety as well as improved patient compliance and adherence, and reduced cost to patients than single drug therapies. From many different perspectives, the development of FDC products is likely a promising approach to achieving clinical benefits and business advantages in many classes of drugs. The rationale for drug combinations can be well established only when the potential benefits are based on valid therapeutic principles and substantiated by clinical evidences. Herein, how combination products can be rationalized, individually or combinedly, with respect to category of therapeutic benefits, class of pharmacokinetic and pharmacodynamics interactions, and type of combination effects is first discussed. Potential limitations of FDC products are to be minimized through a careful assessment of benefits to risks by selecting rational component drugs and their doses as well as by either taking their efficacious interactions and/or avoiding their non-efficacious interactions. A series of step-wise product development strategies are necessary to attain target product profiles of prospective oral FDC products set based on their intended clinical use. This review gives an overview of strategies for formulation development of oral FDC products to be optimized differently depending upon prior knowledge of single products and designated dosage regimens of the FDC products, along with highlighting the current issues and challenges arising in formulation development and evaluation on the performance of FDC products. © 2016, The Korean Society of Pharmaceutical Sciences and Technology.