Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS)

Abstract

In order to investigate the effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in a solid self-nanoemulsifying drug delivery system (solid SNEDDS), different solid SNEDDS formulations were prepared by spray-drying the solutions containing liquid SNEDDS and various carriers. The liquid SNEDDS, composed of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2%w/v flurbiprofen, gave a z-average diameter of about 100nm. Silicon dioxide, a hydrophobic solid carrier, produced an excellent conventional solid SNEDDS with a nanoemulsion droplet size of less than 100nm, similar to the liquid SNEDDS and smaller than the other solid SNEDDS formulations. The drug was in an amorphous state in this solid SNEDDS. Furthermore, it greatly improved the dissolution rate and oral bioavailability of flurbiprofen in rats because it allowed the spontaneous formation of an interface between the oil droplets and the water. Magnesium stearate, a hydrophobic carrier, produced a solid SNEDDS with the largest diameter. However, it greatly enhanced the dissolution rate and oral bioavailability due to the formation of a simple eutectic mixture. The hydrophilic carriers such as polyvinyl alcohol (PVA), sodium carboxymethyl cellulose (Na-CMC) and hydroxypropyl-β-cyclodextrantrin (HP-β-CD) did not form a solid SNEDDS but rather a solid dispersion (or microcapsule). HP-β-CD improved the dissolution rate but did not improve the oral bioavailability as much as the hydrophobic polymers. PVA and Na-CMC hardly improved the dissolution rate but maintained constantly high plasma levels in rats for a long period. Thus, the selection of carrier is an important factor in the development of solid SNEDDS, since the carriers had significant effects on the crystalline properties, dissolution and oral bioavailability of flurbiprofen and on the formation of solid SNEDDS.