Solid Self-Nanoemulsifying Cyclosporine A Pellets Prepared by Fluid-Bed Coating: Stability and Bioavailability Study

Abstract

In previous proof-of-concept study, solid cyclosporine A (CsA) loaded self-nanoemulsifying drug delivery system (SNEDDS) pellets were prepared and characterized in vitro with Labrafil M 1944 CS, Cremophor EL and Transcutol P as oil, surfactant and cosurfactants, respectively. In this study, the stability and the oral bioavailability of the solid CsA SNEDDS pellets were evaluated. The solid CsA SNEDDS pellets, either with or without an outer coating with PVP K30, showed strong moisture absorption under relative humidity (RH) of 75% or 92.5%. The content of CsA in both coated and uncoated pellets varied between 98% and 102% after 10 days in stress testing (high temperature: 60 degrees C or illumination: 4500 lx +/- 500 lx), and between 98% and 104% after two months in accelerated testing (40 degrees C/75%). However, the redispersibility of uncoated solid SNEDDS pellets decreased in both stress and accelerated testing. The oral bioavailability of the coated solid CsA SNEDDS pellets was (74.89 +/- 25.34) % and (81.44 +/- 27.96) % that of its liquid counterpart (the liquid CsA SNEDDS) and Neoral respectively The liquid CsA SNEDDS was bioequivalent to Neoral. The increased particle size due to the impact of constituents of the pellet core might be the main reason for the reduced oral bioavailability. The in vivo performance of the solid SNEDDS pellets can be further improved. The fluid-bed coating technique has considerable potential for use in the preparation of SNEDDS pellets.