Development of softgel capsules containing cyclosporine a encapsulated pine essential oil based self-microemulsifying drug delivery system

Abstract

In this study, a new self-microemulsifying drug delivery system (SMEDDS) based on pine essential oil has been designed and successfully developed to load cyclosporine A (CsA), a poorly water-soluble immunosuppressant, for oral CsA softgel manufacturing. SMEDDS were prepared from pine essential oil and Capmul MCM as oily phases, Kolliphor RH 40 as surfactant, polyethylen glycol 400 as co-surfactant/co-solvent and none volatized co-solvent utilizing the pseudo-ternary phase diagrams. CsA SMEDDS loading 9.09% of CsA, dispersed in aqueous environments (water, pH 1.2, 4.5 and 6.8 buffers), presented an average droplet size of about 160 nm with polydispersity index (PdI) below 0.25, and were stable after 6 h of self-emulsification. Cytotoxicity of CsA SMEDDS on LLC-PK1 cells demonstrated that CsA SMEDDS had an IC50 value greater than that of the reference product, suggesting product safety against nephrotoxicity. CsA SMEDDS was filled into oval-5 soft gelatin capsules (softgels) containing 0.5% glycine which could avoid the cross-linking process. Additionally, CsA SMEDDS softgels presented the in vitro release profiles equivalent to that of Sandimmun Neoral® at pH 1.2, 4.5 and 6.8. Therefore, the pine essential oil based SMEDDS was considered to be potential and suitable for developing softgels to enhance the oral bioavailability of CsA.