The objective of this work is to (i) study the effect of variations in the proportions of four Macrogols on the pharmaco-technical characteristics of suppositories, (ii) define the optimal formula for a suppository with immediate effect; maximum disintegration and a minimum of hardness as defined in the European Pharmacopoeia. The lattice design mixture has been proposed as an optimization technique, the formulation factors are presented by the proportions of PEG 400 (X1), PEG 600 (X2), PEG 4000 (X3) and PEG 6000 (X4) and the response variables are (i) the disintegration time (Y1) (ii) the hardness (Y2). The second-degree empirical model was postulated to model the variations of the two response variables using the least-squares method.  The selected model explained about 67% and 84% of the variation for Y1 and Y2, respectively. All four factors had significant effects on the properties of the suppository. Interactions negatively affected both responses.  The numerical desirability method gave the following optimal formula: PEG400 (28.71334 %); PEG600 (24.23773%), PEG4000 (35.00944%) and PEG6000 (12.03949%) for a disintegration of 25.839 (+/-2.3) min and hardness =2147.321 (+/- 50) g.