For Singulair® granules, the AUC0–4 h in vitro of the direct administration of formulation profile was significantly lower compared with the ones of the co-administration with drinks profiles (milk and formula), and significantly higher than the one of the co-administration with applesauce profile. Drug dissolution (4 h) was higher when the formulation was co-administered with milk (74.3 and 93.0% drug dissolved in Pi-FaSSGF/FaSSIF-V2 and Pi-FaSSGF/Pi-FeSSIF, respectively), than when mixed with formula (% drug dissolved = 37.4 (Pi-FaSSGF/FaSSIF-V2) and 55.3 (Pi-FaSSGF/Pi-FeSSIF)). These results confirm that vehicles of the same subtype (i.e. dairy drinks) can have different effects on drug dissolution, in accordance with what was observed in previous studies (12,13,26). The lower dissolution of montelukast observed when the granules were mixed with formula, compared with the drug dissolution when mixed with milk, relates to the differences in the solubility of montelukast in the two vehicles (milk: 13.3 mg/mL; formula: 12.0 mg/mL) (13). It can be hypothesised that these differences were accentuated by the use of different volumes of the two drinks mixed with the formulation (15 mL milk and 5 mL formula). This is of particular importance considering that the recommendations for medicine co-administration with drinks/soft foods often do not specify the volume of vehicle to use (7). These results indicate the risk of unspecific recommendations for vehicle choice, and further confirm the importance of the FDA draft guidance on vehicle selection and in vitro methods for product quality assessment (9). The lowest % drug dissolution (4 h) was observed for the mixing with applesauce scenario (% drug dissolved = 9.8 (Pi-FaSSGF/FaSSIF-V2) and 18.1 (Pi-FaSSGF/Pi-FeSSIF)). The solubility of montelukast in this vehicle is 5.3 mg/mL, and the pH of the vehicle is ~ 3, which might partly have contributed to the lower drug dissolution observed when the granules were mixed with applesauce, in comparison with when the formulation was mixed with formula and milk. However, the lower % drug dissolution is likely more related to the presence of starch in the composition of applesauce, which forms a net gel around the formulation and negatively affects drug release and dissolution (27). During the dosing preparation and dissolution testing, it was observed that the applesauce-granules mixture was more viscous than the formula/milk-drug mixtures. While the mixture would eventually slowly disperse once added to the media, it is not possible to distinguish the formulation from the vehicle mixture during the in vitro study.