Poly(vinyl alcohol) as Emulsifier Stabilizes Solid Triglyceride Drug Carrier Nanoparticles in the alpha-Modification

Colloidal dispersions of solid lipids are under intensive investigation as drug delivery systems. In the present :study, polyvinyl alcohol) (PVA) was tested as an alternative stabilizer for triglyceride nanoparticles. The dispersions contained 10% triglyceride (trimyristin or tristearin) and 5% PVA and were prepared by high pressure melt homogenization. The nanoparticle dispersions were investigated for their thermal behavior and storage stability with special regard to the polymorphic transitions of the triglyceride matrix, including effects of storage temperature and the incorporation of model drugs (diazepam, ubidecarenone) using photon correlation spectroscopy, differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy. The release of the model drug diazepam from a selected nanoparticle dispersion was investigated with differential pulse polarography. Triglyceride nanoparticles prepared with PVA displayed an unusually high stability of the metastable alpha-modification depending on the type of triglyceride and the storage conditions. In tristearin nanoparticles, the alpha-polymorph was stable for at least 9 months at refrigerator temperature and the particles exhibited a spherical shape in electron microscopic investigations. Moreover, the a-form in PVA-stabilized tristearin nanoparticles seemed to be; highly disordered, as it did not lead to a pronounced small-angle X-ray reflection. Storage at higher temperatures led to a transformation of the particles into the beta-modification, which usually was accompanied by an increase in particle size. Incorporation of the two model drugs did not change the crystal modification of the particle matrix to a large extent. After dilution into a large volume of release medium, a large fraction of the model drug diazepam was released immediately but there was no further release over several hours. The high stability of PVA-stabilized tristearin nanoparticles with regard to particle size and alpha-modification makes them suitable as a model for investigations on the influence of the polymorphic form (e.g., in comparison with nanoparticles in the more stable beta-modification) on pharmaceutically important parameters such as drug load and drug release.