Influence of composition and preparation parameters on the properties of aqueous monoolein dispersions.

Colloidal cubic phase particles formed in the monoolein/poloxamer/water system are being investigated as potential drug carriers for, e.g., intravenous administration. Preparation methods must, however, still be further developed to reliably yield monoolein dispersions with cubic particles in a size range acceptable for i.v. administration and adequate long-term stability. In this context, the influence of different composition and preparation parameters on the properties of monoolein dispersions prepared by high-pressure homogenization was studied. High pressure homogenization of coarse poloxamer 407-stabilized monoolein/water mixtures leads to dispersions with a large fraction of micrometer-sized particles at low poloxamer concentrations. Higher poloxamer concentrations lead to lower mean particle sizes but the fraction of cubic particles becomes smaller and vesicular particles are observed instead. A study of the characteristics of a dispersion with a standard composition indicated that the homogenization temperature has a much stronger influence on the dispersion properties than the homogenization pressure or the type of homogenizer used. Temperatures around 40-60 degrees C lead to the most favorable dispersion properties. The high temperature sensitivity of the preparation process appears to be at least partly correlated with the phase behavior of the dispersed particles determined by temperature-dependent X-ray diffraction.

Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration.

Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS), was found to be between 60 and 260 nm in the investigated range of CMZ concentrations, highly dependent on the concentration, but more weakly so on the number of homogenisation steps. Slow-scanning high-sensitivity differential scanning calorimetry (DSC) measurements showed that CMZ depresses the phospholipid chain melting temperature in the emulsion system, whereas (13)C nuclear magnetic resonance (NMR) experiments suggested that the CMZ molecules are to a large extent located in the surface region of the emulsion droplets. This interpretation is compatible with results from NMR self-diffusion measurements, which showed that most of the CMZ molecules are rapidly exchanged between emulsion droplets and the aqueous surrounding. It can be concluded that the surface-active drug CMZ has a significant influence on the characteristics of phospholipid-stabilised emulsions through its ability to interact with the phospholipid interface. Thus, the results underline the importance of characterising drug-lipid interactions for the development of lipid-based formulations.

Preparation and physicochemical characterization of aqueous dispersions of coenzyme Q10 nanoparticles.

The present study describes a novel pharmaceutical formulation of coenzyme Q10, viz. submicron-sized dispersions of the substance prepared by emulsification of molten coenzyme Q10 in an aqueous phase. Photon correlation spectroscopy reveals mean diameters of 60 to 300 nm depending on process parameters. Coenzyme Q10 nanoparticles remain stable on storage for more than 30 months. Lipophilic drugs can be incorporated into the nanoparticles demonstrating their potential use as a drug carrier system. Transmission electron micrographs of freeze-fractured replica show spherical particles with an amorphous core. Cryo-electron microscopy reveals the coexistence of small unilamellar vesicles in phospholipid stabilized dispersions. Thermoanalysis and X-ray studies indicate that the dispersed and emulsified coenzyme Q10 does not recrystallize even at 4 degrees C over 30 months. These agree with 1H NMR data which demonstrate that coenzyme Q10 molecules have a high mobility when formulated as nanoparticles and that colloidally dispersed coenzyme Q10 remains in the state of a supercooled melt. Despite the high melting point of the bulk material, coenzyme Q10 dispersions represent no suspensions but O/W emulsions according to the IUPAC definition (1).