Development of solid lipid nanoparticles for enhanced solubility of poorly soluble drugs

Cyclosporine (CyA) solid lipid nanoparticles were prepared by using a solvent free high pressure homogenization process. CyA was incorporated into SLNs that consisted of stearic acid, trilaurin or tripalmitin lipid solid cores in order to enhance drug solubility. The process was conducted by varying lipid compositions, drug initial loading and applied homogenization pressure. The processing temperatures were above the lipid melting points for all formulations. The empty and CyA loaded SLN particles made were characterized for particle size stability over six months. Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) showed particle sizes ranging from 112-177 nm for empty and 181-215 nm for loaded SLNs each with narrow particle size distributions. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques were used to characterize the CyA state, which was found to be amorphous, within the lipid cores of freeze-dried SLNs. The CyA metastable form showed a profound effect on the drug dissolution rates. SLNs were incubated in Caco-2 cells for 24 hr showing negligible cell cytotoxicity up to 15 mg/ml.