Design and evaluation of solid self-nanoemulsifying drug delivery systems of cyclosporine developed with a superior adsorbent base†

Abstract

Cyclosporine (CYC) is a drug that belongs to the BCS class II category. This study was designed to develop novel solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for cyclosporine (CYC), using chitosan–EDTA microparticles. Such microparticles are known to exhibit superior adsorbent characteristics and were prepared by two different methods viz. spray drying (SD-CHEM) and solvent evaporation (SE-CHEM). Capmul® GMS-50K, Labrafac, and PEG 400 were chosen as the oil, surfactant, and co-surfactant, respectively. The cyclosporine liquid self-nanoemulsifying drug delivery system (CYC-L-SNEDDS) was developed with an optimal oil to S_mix (surfactant : co-surfactant) ratio of 40 : 60, determined through a pseudo ternary phase diagram. The novel S-SNEDDS were developed by adsorbing CYC-L-SNEDDS onto the chitosan–EDTA microparticles, resulting in CYC-SD-S-SNEDDS and CYC-SE-S-SNEDDS. Both formulations exhibited favorable drug loading, with 81.184 ± 4.191% for CYC-SD-S-SNEDDS and 56.426 ± 5.471% for CYC-SE-S-SNEDDS. XRD and DSC confirmed drug amorphization, while SEM revealed a smooth, well-distributed adsorbate on the adsorbent surfaces, with particle sizes of 5–8 μm for CYC-SD-S-SNEDDS and 10–12 μm for CYC-SE-S-SNEDDS. When tested for stability, the developed formulations exhibited excellent physical and thermodynamic stability. The globule size for CYC-SD-S-SNEDDS was 138.7 ± 4.14 nm, with a PDI of 0.613 ± 0.004, while CYC-SE-S-SNEDDS had a globule size of 166.9 ± 4.04 nm and a PDI of 0.579 ± 0.003. The results of in vitro dissolution studies revealed that there was a fourfold increase in drug dissolution for CYC-SD-S-SNEDDS (80.03%) and CYC-SE-S-SNEDDS (72.26%) when compared to the pure cyclosporine (19.8%). A similar pattern was observed in ex vivo permeation studies where CYC-SD-S-SNEDDS showed 39.34% release and CYC-SE-S-SNEDDS exhibited 28.31% release as compared to CYC-L-SNEDDS (41.46%). Furthermore, CYC-SD-S-SNEDDS outperformed CYC-SE-S-SNEDDS, indicating the superiority of microparticles developed by the spray drying method (SD-CHEM) as adsorbents for solidification. These findings suggest enhanced dissolution and permeation for cyclosporine in S-SNEDDS.