In pharmaceutical industries, the formulator is usually faced with the optimisation of the excipient mixture composition aimed to prepare a product with the required characteristics. Experimental research methodology represents an efficient approach for solving such optimisation problems. Planning mixture experiments using specific designs allows to analyse the blending properties of each mixture component and estimate an empirical model approximating the response of interest as a function of excipient proportions. In this study the evolution of theophylline solubility in a four-component system with constraints was analysed using two mixture design approaches: a classical mixture component proportion approach and a mathematically independent variable approach. An optimal region characterised by high solubility values was found and further explored in order to verify the insensitivity of theophylline solubility to slight variations of the excipient mixture composition.