The expulsion of lipophilic drugs from the cores of solid lipid microspheres in diluted suspensions and in concentrates

The aim of the study was to compare incorporation of bupivacaine base, bupivacaine stearate and indomethacin in diluted suspensions of lipospheres (10%, w/w of lipid) and in concentrates (50%, w/w of lipid). The lipid cores were composed of a mixture of solid and liquid triglycerides (Precirol and Miglyol 4:1). The lipospheres sizing between 0.5–10 μm (suspensions) and 0.5–20 μm (concentrates) were prepared using a hot emulsification with high-shear mixing and cold resolidification method. None of the studied drugs was successfully incorporated in the lipid core. The increased incorporation of drugs determined in the concentrated lipospheres was only apparent, since in fact all the dose was only attached to the surface of the lipid particles and was transferred to the aqueous phase in the course of an intensive agitation. The presence of hydrophilic polymers in the aqueous phase did not prevent the expulsion effect although drug precipitation was retarded. The expulsion effect did not correlate with the solubility of drugs determined in the bulk lipids.