Preparation of Powdered Phospholipid Nanospheres by Fluidized-Bed Granulating in an Aqueous System with Sugars

Abstract

Phospholipid nanosphere dispersions incorporating a lipophilic drug were prepared by the heating method. Prepared dispersions were powdered by depositing them on sugar nuclei in a fluidized-bed granulator in an aqueous system. Resultant free-flowing powders, which were agglomerates of sugar with phospholipid, reproduced phospholipid nanosphere dispersions when rehydrated with water. Incorporation of a lipophilic drug, e.g., tocopherol, into the nanospheres or increasing of phospholipid concentration in the formulation increased the sizes of rehydrated nanospheres compared to the original dispersion before powdering due to the fusion or aggregation of the nanospheres. Proper selection of sugar nuclei, decreasing the sizes of original phospholipid nanospheres for powdering and addition of polyhydric or sugar alcohols into the sprayed dispersion, however, significantly reduced the aggregation of rehydrated nanosphere. All procedures from the preparation of the original nanosphere dispersion to its powdering were performed in an aqueous system without use of any organic solvent. The procedures described here are recommended to produce stable powdered nanosphere which can be rehydrated to form phospholipid nanosphere dispersions when required.