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Solid phospholipid (PL) nanoparticles with griseofulvin (GRIS) as a model drug were prepared by co-spray drying. Their dissolution properties were compared with formulations containing the physical blends of the native crystalline drug and excipient materials, and physical blends of the spray dried materials. Co-spray drying was performed from ethanol + water solutions (80 + 20) using Büchi Nano Spray Dryer B-90. Dissolution profiles in phosphate buffer (PBS), simulated intestinal fluids (fasted state simulated intestinal fluid (FaSSIF)) and pancreatin containing media (PAN) were studied. It was found that the influence of PL on the dissolution profile was affected by both the solid state of the drug formulation and the dissolution medium: the co-SD formulations showed the fastest release in all media. The amount of GRIS dissolved after 5 h increases by a factor of 7 for the co SD as compared to physical blend of native materials in PBS, and a factor of 4 in FaSSIF respectively. Surprisingly, in contrast to PBS, dissolution rate in FaSSIF decreased with increasing the PL content. All the pancreatin containing media showed a decrease in dissolution rate and extent independently of the processing methods due to an incompatibility between GRIS and PAN.