Fixed-dose Combination Medicinal Products: the Role of Modern Pharmaceutics

Abstract

Fixed-dose combination (FDC) medicinal products are combinations of two or more active ingredients in a fixed ratio of doses in a single dosage form (tablets, capsules, etc.). Clinical studies have shown that FDC products have several therapeutic advantages, such as improved adherence, reduced risk of side effects and lower overall costs. FDC products are often preferred to using multiple single-substance dosage forms or packaging multiple dosage forms for prescription, due to decreased pill-burden and better patient adherence to dosing instructions and compliance. FDC products also bring financial benefits from reduced production costs and convenience in distribution and usage. However, the development and application of FDC medicinal products face many challenges. When combining multiple substances in a dosage form, each with different physicochemical and biopharmaceutical properties, advanced technologies are needed to ensure the required release and absorption of drugs. The interactions between ingredients also pose a significant challenge in formulation design and processing. Analytical methods used in evaluation and testing of FDC drugs are also more complex than for single-substance dosage forms. Despite these challenges, FDC medicinal products provide great benefits in clinical practice, and have seen continual development in recent years. This review highlights modern technologies applied to the development and manufacturing of FDC medicinal products, including coating technology, multilayer tableting, controlled drug-release systems, hot-melt extrusion, 3D-printing technology. It also presents examples of technological applications in the development of FDC products for treatment of certain diseases, such as diabetes, cardiovascular diseases, and viral infections.

Keywords: Fixed-dose combination, polypill capsules, multilayer tablets; gastric retention of oral dosage forms; hot-melt extrusion; three-dimensional (3D) printing.