Abstract This work deals with the development and implementation of mathematical models in the General Algebraic Modeling System (GAMS) environment for optimization purposes, involving extrinsic functions that are executed outside GAMS from dynamic-link libraries (DLL) implemented in the programming language C. Three DLL libraries are developed to calculate thermodynamic properties: the Raoult's law for vapor-liquid equilibrium, the Non-Random Two-Liquid (NRTL) model, and the Peng–Robinson equation of state. A detailed description on how GAMS and DLL libraries interact is presented. Case studies dealing with the optimal design of multi-component distillation columns with increasing complexity levels are discussed. For the proposed case studies, the obtained results show that the usage of the proposed extrinsic functions allows to significantly enhance the model implementation compared to the traditional model implementation approach, and to considerably reduce the model size as well as the computational time required by the optimization algorithms.