Solid self-nanoemulsifying drug delivery systems of nimodipine: development and evaluation

Background

This study aimed to formulate solid self-nanoemulsifying drug delivery systems (SNEDDS) for nimodipine (NIM). The selection of Cremophor RH 40, Lipoxol 300, and PEG 400 as oil, surfactant, and co-surfactant was based on solubility and self-emulsification assessments. A ternary phase diagram determined the optimal oil to Smix (surfactant/co-surfactant) ratio (40:60). By utilizing liquid SNEDDS (NIM-SNEDDS) as an adsorbate and chitosan EDTA microparticles, developed through spray drying (SD-CHEM) and solvent evaporation (SE-CHEM) as adsorbents, the solid SNEDDS were created (NIM-SD-SSNEDDS and NIM-SE-SSNEDDS, respectively).

Results

Both solid formulations exhibited favourable drug loading (NIM-SD-SSNEDDS = 79.67 ± 2.97%, NIM-SE-SSNEDDS = 77.76 ± 4.29%), excellent flowability, and drug amorphization as per XRD and DSC analysis. Scanning electron microscopy revealed smoothening and filling of adsorbent surfaces by adsorbate (with size range NIM-SD-SSNEDDS = 10–15 μm, NIM-SE-SSNEDDS = 20–25 μm). FTIR confirmed no interaction of drug and excipients. Stability studies demonstrated the physical and thermodynamic stability of reconstituted nanoemulsions with droplet size, PDI, zeta potential, emulsification time, % transmittance and cloud temperature for NIM-SD-SSNEDDS as 247.1 nm, PDI 0.620, 1.353 mV, 38–41 s, 94.64%, 54 °C and for NIM-SE-SSNEDDS as 399.6 nm, PDI 0.821, 1.351 mV, 40–48 s, 92.96%, 49 °C, respectively. FE-SEM images showed globules formed with small sizes, and there was no coalescence evidence, implying the reconstituted nanoemulsions' stability. In vitro dissolution studies revealed a fourfold increase in drug dissolution for NIM-SD-SSNEDDS (84.43%) and NIM-SE-SSNEDDS (76.68%) compared to pure drug (28%). Ex vivo permeation studies indicated almost similar profiles for NIM-SD-SSNEDDS (22.61%) and NIM-SE-SSNEDDS (21.93%) compared to NIM-SNEDDS (25.02%).

Conclusion

NIM-SD-SSNEDDS exhibited superior performance compared to NIM-SE-SSNEDDS, highlighting the efficacy of microparticles developed by the spray drying method (SD-CHEM) as adsorbents for solidification. These results suggest enhanced dissolution and permeation for nimodipine in both the solid SNEDDS.