The development of innovative forms of combination drugs is closely related to the invention of the multilayer tablet press, polymers for pharmaceutical applications, the hot-melt extrusion process, and 3D printing in the pharmaceutical industry. However, combining multiple drugs within the same dosage form can bring many physicochemical and pharmacodynamic interactions. More and more new forms of fixed-dose combinations (FDCs) have been developed due to work to overcome the incompatibility of active substances or to obtain different drug release profiles in the same dosage form. This review provides discussions of the application of various innovation formulation technologies of FDC drugs such as bilayer system, multilayer tablet, active film coating, hot-melt extrusion, and 3D printing, taking into account the characteristics of the key ingredients in the FDC formulation and presenting technological problems and challenges related to the development of combination drugs. Moreover, the article summarizes the range of dosage forms that have been made using these technologies over the past 30 years.

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.