Evaluation of nano spray-drying as a two-step method for solid lipid nanoparticle dry powder fabrication

In this study, the nano spray-drying technique [1-3] was investigated as an innovative two-step method to produce solid lipid nanoparticles (SLN) in the form of a dry powder. Compritol was chosen as wall-forming lipid due to its biocompability and high melting point. Cetyl palmitate was also examined for comparison. The SLN were fabricated as SLN embedded leucine microparticle (SLN-LM) dry powder. Briefly, an O/W emulsion of lipid dissolved in chloroform and a surfactant plus L-leucine aqueous solution was prepared using Ultra-Turrax. A screening on emulsification conditions was performed in order to establish optimal lipid concentration and type of surfactant. The best emulsion was obtained by using Lutrol as a surfactant and 125 mg/mL lipid concentration. Formulation and spray-drying factor effects on the obtained particles were evaluated by a two-step experimental design approach: step 1) a 2-level fractional factorial design was employed to determine the most influential factors; step 2) the design was extended over a previously determined working space by reducing the number of factors. Compritol concentration, L-leucine/lipid ratio and Lutrol concentration resulted the most relevant factors. Spray-drying parameters were less relevant. The best features in terms of morphology, SLN fraction and size obtained from the first design were achieved using 125 mg/mL Compritol, 1.5% w/v Lutrol and 1:1 lipid/L-leucine ratio, while the spray-drying conditions were 110°C inlet temperature, 100 L/min air flow rate and 50 mbar pressure. The composite particles were regular with a mean size of 1.1 ± 0.3 μm and a SLN population around 150 nm. However, yield was as low as 10%. In this regard, the second design step allowed to reach 51% yield, 3.2 ± 1.8 μm SLN-LM size by maintaining the same SLN population around 150 nm. Such a result was achieved by reducing Compritol concentration to 40 mg/mL and decreasing lipid/L-leucine ratio to 1:3, using 95°C inlet temperature, 100 L/min air flow rate and 40 mbar pressure. Although the obtained SLN-LM were larger and less regular, such conditions were considered an acceptable compromise between SLN size distribution, morphology and yield. Increase in Lutrol concentration or the use of cetyl palmitate worsened SLN features and particle homogeneity. An improvement in the emulsification step was identified as a key factor for future successful development of the method.