The components of the self-emulsifying formulations i.e., oil, surfactant, co-surfactant should have good solvent properties and appear as monophasic liquid at ambient temperature.28 A solubility study of ISR in various lipid vehicles plays a vital role in selection of components with maximum solubilizing capacity for developing a minimal volume of SNEFs with optimum drug loading.29,30
The solubility study results of ISR in various vehicles shown in Table 3, suggest that Lauroglycol FCC (1.67±0.16mg/mL) and Acconon E (1.15±0.24mg/mL) exhibited lowest drug solubility. It is also evident that among the tested vehicles ISR has highest solubility in Cremophor EL (>300 mg/mL). Furthermore, higher solubility was also observed in Capmul MCM L8 (18.73±0.21 mg/mL) and Labrafil M 2125 CS (6.52 ±0.21 mg/mL) compared to other vehicles. Based upon highest ISR solubility, Labrafil M 2125 CS, Capmul MCM L8 and Cremophor EL were selected as the oil phase, surfactant and co-surfactant, respectively, for formulation of SNEFs. Labrafil M 2125 CS with HLB 4 was selected as oily phase due to its good solubilizing ability for poorly soluble lipophilic drugs,31 emulsion forming capacity and its bioavailability enhancing properties by lymphatic absorption.
Ternary phase diagram
A series of SNEFs were prepared using Labrafil M 2125 CS (Oil), Capmul MCM L8 (surfactant) and Cremophor EL (co-surfactant) with high drug solubility and tested for phase behavior. An earlier report suggests that combination of surfactant with cosurfactant is more effective in producing emulsion with small globule size than surfactant alone.32 A ternary phase diagram (Figure 1) was constructed based on the results of phase behavior studies to optimize the concentration of oil, surfactant and co-surfactant in the development of SNEF and to identify the stable emulsifying region. The colored region in the Figure 1 shows formation of emulsion systems upon dispersion in aqueous medium at ambient temperature.
All the prepared formulations showed spontaneous formation of emulsion and initially all the emulsions formed were clear and stable without any signs of phase separation or precipitation. Surfactant and co-surfactants present in the formulation were favorably adsorbed at oil/water interface thus reducing the surface free energy of formation of emulsion and also prevent coalescence of dispersed droplets. This phenomenon improves spontaneity of emulsification and its thermodynamic stability.33,34
The resultant emulsions were observed for clarity and stability after 48 h. It was observed that formulations with S/CoS ratio of 1:1 that are F1, F2 and F3 produced stable clear emulsions whereas the emulsions of formulations with S/CoS ratio of 3:1, 5:1 turned to slightly turbid with signs of phase separation and precipitation. From these results it is concluded that the formulations with co-surfactant (Cremophor EL) concentration more than 33.3% were showing good emulsification...