The aim of the work was to prepare and characterize lipid nanoparticles (NPs) and to investigate the possibility of obtaining a redispersible powder, preferable due to its superior stability. To this aim, both lyophilisation and spray-drying were investigated. Experimental Polysorbate 80 stabilized cetylpalmitate (CP) NPs were prepared using the hot high pressure homogenization technique. Particle size was determined with photon correlation spectroscopy, using a Nicomp 380 autocorrelator equipped with a Coherent Innova 70-3 argon ion laser. The suspension was then dried using both freeze-drying (Benchtop 2K, Freeze Dry VirTis) and spray-drying (nano spray-dryer B90, Büchi). Prior to drying, lipid NP suspensions with a volumetric fraction of 0.121 were appropriately diluted (1:5, 1:10, and 1:20) and ethanol, trehalose, and polyethylene glycol (PEG) have been added to evaluate their usefulness in avoiding irreversible aggregation during water removal. After drying, the obtained powder was dispersed in ultrapure water under stirring and submitted to particle size analysis to evaluate aggregation. Size increase after drying was expressed as Δsize calculated using the following equation. Results Lipid NPs were successfully produced and characterized by dimensions suitable for parenteral administration. In fact, the mean hydrodynamic diameter (MHD) was around 180 nm. After freeze-drying, an increase of MHD has been observed in all cases and in absence of additives a MHD > 2 μm was recorded even at the highest dilutions. Among additives, trehalose was the most successful in reducing aggregation. Using trehalose and 1:20 dilution, a Δsize of 18% (MHD = 199 nm) was obtained. Satisfactory results were also obtained for the other dilutions (Δsize = 28 or 39%), while the addition of ethanol worsen the situation. With PEG, MHD comprised between 269 and 290 nm were obtained using water/ethanol dilution (61<Δsize<73). In the case of spray-drying, an instrument of new generation, in which the powder recovery mechanism is completely different from the conventional instruments, was employed. Without additive, the small fraction of powder that was recovered was characterized by large particle size. As in the case of freeze-drying, the use of additives appeared to be essential to limit lipid NP aggregation. Also with spray-drying, the best results were obtained with threhalose as additive and when dilution was performed with an ethanol/water mixture with respect to water. Using the solvent mixture, the inlet temperature in the instrument can be set to lower values, limiting the effect of temperature on lipid NP aggregation. With trehalose, Δsize of 20, 34 and 106% were registered for 1:20, 1:10 and 1:5 dilutions, respectively. The Δsize was almost doubled when water was used to dilute the suspensions. Unfortunately, the Δsize with PEG was always higher than 150% except for the 1:20 water dilution where lipid NPs were characterized by a MHD of 330 nm (Δsize of 98%). Conclusions Both freeze-drying and spray-drying can be used to obtained an easy redispersible powder starting from lipid colloidal suspension. Besides, working conditions (e.g., additives, dilution) have to be accurately chosen to limit particle growing and/or sintering. In the present study, high dilutions and trehalose showed the overall best performance in lipid NP drying.

Freeze-drying and spray-drying of lipid nanoparticle suspensions

BLASI, PAOLO;SCHOUBBEN, Aurelie Marie Madeleine;GIOVAGNOLI, Stefano;RICCI, Maurizio
2012

Abstract

The aim of the work was to prepare and characterize lipid nanoparticles (NPs) and to investigate the possibility of obtaining a redispersible powder, preferable due to its superior stability. To this aim, both lyophilisation and spray-drying were investigated. Experimental Polysorbate 80 stabilized cetylpalmitate (CP) NPs were prepared using the hot high pressure homogenization technique. Particle size was determined with photon correlation spectroscopy, using a Nicomp 380 autocorrelator equipped with a Coherent Innova 70-3 argon ion laser. The suspension was then dried using both freeze-drying (Benchtop 2K, Freeze Dry VirTis) and spray-drying (nano spray-dryer B90, Büchi). Prior to drying, lipid NP suspensions with a volumetric fraction of 0.121 were appropriately diluted (1:5, 1:10, and 1:20) and ethanol, trehalose, and polyethylene glycol (PEG) have been added to evaluate their usefulness in avoiding irreversible aggregation during water removal. After drying, the obtained powder was dispersed in ultrapure water under stirring and submitted to particle size analysis to evaluate aggregation. Size increase after drying was expressed as Δsize calculated using the following equation. Results Lipid NPs were successfully produced and characterized by dimensions suitable for parenteral administration. In fact, the mean hydrodynamic diameter (MHD) was around 180 nm. After freeze-drying, an increase of MHD has been observed in all cases and in absence of additives a MHD > 2 μm was recorded even at the highest dilutions. Among additives, trehalose was the most successful in reducing aggregation. Using trehalose and 1:20 dilution, a Δsize of 18% (MHD = 199 nm) was obtained. Satisfactory results were also obtained for the other dilutions (Δsize = 28 or 39%), while the addition of ethanol worsen the situation. With PEG, MHD comprised between 269 and 290 nm were obtained using water/ethanol dilution (61<Δsize<73). In the case of spray-drying, an instrument of new generation, in which the powder recovery mechanism is completely different from the conventional instruments, was employed. Without additive, the small fraction of powder that was recovered was characterized by large particle size. As in the case of freeze-drying, the use of additives appeared to be essential to limit lipid NP aggregation. Also with spray-drying, the best results were obtained with threhalose as additive and when dilution was performed with an ethanol/water mixture with respect to water. Using the solvent mixture, the inlet temperature in the instrument can be set to lower values, limiting the effect of temperature on lipid NP aggregation. With trehalose, Δsize of 20, 34 and 106% were registered for 1:20, 1:10 and 1:5 dilutions, respectively. The Δsize was almost doubled when water was used to dilute the suspensions. Unfortunately, the Δsize with PEG was always higher than 150% except for the 1:20 water dilution where lipid NPs were characterized by a MHD of 330 nm (Δsize of 98%). Conclusions Both freeze-drying and spray-drying can be used to obtained an easy redispersible powder starting from lipid colloidal suspension. Besides, working conditions (e.g., additives, dilution) have to be accurately chosen to limit particle growing and/or sintering. In the present study, high dilutions and trehalose showed the overall best performance in lipid NP drying.
2012
889603809X
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1009066
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