Embedding lipid nanodispersions in matrices: preparation of solid dosage forms with high lipid content and structural investigations using atomic force microscopy

Herrmann, Fabian C.; Hofmann, Nicole; Haslacher, Fiona; Steiner, Denise

Abstract

Lipid nanodispersions are a promising formulation strategy for improving the bioavailability of drugs that are poorly water-soluble but highly lipophilic. Since patients prefer solid dosage forms, further processing of the liquid formulations is necessary. In order to expand the range of applications for drugs formulated in lipid nanodispersions, a high lipid content is required in the solid dosage forms. The aim of the current study was to determine the maximum loading capacity of lipid nanoemulsions and nanosuspensions by embedding the dispersions into orodispersible films and lipid-containing powders using spray drying. Atomic force microscopy enabled an assessment of the particle arrangement in the solid dosage forms and identified a stack-like orientation of the platelet-shaped triglyceride particles when embedded in orodispersible films. During the preparation of the powders by spray drying, a random particle arrangement was achieved, which was caused by the melting of the lipid particles during processing. Furthermore, atomic force microscopic images showed that tristearin particles in the metastable α-modification can exist in elongated to platelet-like shape traced back to the particle formulation and preparation process. The highest loading capacity in the solid dosage forms was achieved when the lipid nanodispersions were embedded in a film-forming matrix of PVA, resulting in lipid contents of up to 47 wt.%. Similar high lipid contents were achieved when lactose was used as the matrix material during spray drying.