2.2.1. Preparation of Liquid Emulsions

The liquid emulsion composition (selection of components) and preparation were based on results from a previous article and modified in order to include insoluble matrix formers [12]. Briefly, 1OG was heated up to 40 °C in order to obtain a clear liquid and mixed with M812 in the ratio of 9:1. Tween^® 20 was added to the prepared mixture up to 0.5% (m/m) and then mixed. After the oil–surfactant solution was prepared, simvastatin in the amount of 70 mg per gram of oil–surfactant solution, was added, dispersion heated to 37 °C and mixed with magnetic stirrer until a clear solution was obtained. The oil–surfactant mixture drug solution, referred as the oil phase, was kept at 37 °C.

The composition of the external—matrix phase and its ratio to the oil phase was varied according to the experimental design described in Section 2.3. The mannitol solution was heated to 37 °C and the oil mixture was added during stirring with propeller agitator at 640 rpm. The resulting pre-emulsion was firstly homogenised using a high shear, rotor–stator, homogeniser (Ultra-Turrax^® T25, IKA-Works, Staufen, Germany) for 5 min at 8000 rpm and 3 min at 12,000 rpm. HPMC (hydroxypropyl methylcellulose) was prepared as a separate solution to prevent HPMC chain degradation during high shear, rotor–stator homogenization [47,48]. The HPMC solution was added to pre-emulsion during mixing with propeller agitator at 640 rpm for 3 min. Finally, a two-stage high pressure homogeniser (APV—2000, SPX flow technologies, Silkeborg, Denmark), with 300 bar for the first stage was used in order to obtain the emulsion. The high pressure homogenisation was repeated nine times. Depending on the experimental design, MS or NCC in powder, alone or in combination, was added to the prepared emulsion. After the addition of the two insoluble matrix formers, the final emulsion was mixed with propeller agitator at 640 rpm for 2 more hours.