The effect of incorporating caffeine and paracetamol on the structure and behaviour of Gelucire 50/13 has been studied with a view to establishing whether the choice of drug influences the solid structure and release mechanism. Dispersions containing up to 30% w/w drug were prepared and studied using differential scanning calorimetry (DSC), hot stage differential interference contrast microscopy (HSM), dissolution studies and erosion, water uptake (WU) and diameter change measurements. Gelucire 50/13 alone showed a broad melting endotherm using DSC, with two dominant peaks at 36 and 44 °C. While incorporation of caffeine did not result in marked changes to the profile, the presence of paracetamol increased the proportion of material in the lower melting peak. HSM studies indicated that the Gelucire crystallised into two main spherulitic conformations; paracetamol appeared to act as a nucleation site for the lower melting fractions while caffeine particles changed into a needle-shaped morphology on cooling the system from the liquid state. Dissolution studies at 37 °C showed the caffeine to be released at a relatively faster rate than the paracetamol. Kinetic modeling and direct measurement of the erosion profile indicated that the caffeine systems showed a greater preponderance for erosion than did the corresponding paracetamol systems. It is suggested that the paracetamol promotes the generation of the lower melting form of Gelucire 50/13 which in turn influences the release rate and mechanism. The study therefore indicates that the influence of the drug should be carefully considered when studying Gelucire matrix systems.