Novel lipid-based colloidal dispersions as potential drug administration systems - expectations and reality

Colloidal drug carriers offer a number of potential advantages as delivery systems for, for example, poorly soluble compounds. The first generation of colloidal carriers, in particular liposomes and sub: micron-sized lipid em ulsions, are, however, associated with several drawbacks which so far have prevented the extensive use of these carriers in drug delivery. As an alter native colloidal delivery system melt-emulsified nanoparticles based on sol id lipids have been proposed. Careful physicochemical characterization has demonstrated that these lipid-based nanosuspensions (solid lipid nanopartic les) are not just "emulsions with solidified droplets". During the developm ent process of these systems interesting phenomena have been observed, such as gel formation on solidification and upon storage, unexpected dynamics o f polymorphic transitions, extensive annealing of nanocrystals over signifi cant periods of time, stepwise melting of particle fractions in the lower-n anometer-size range, drug expulsion from the carrier particles on crystalli zation and upon storage, and extensive supercooling. These phenomena can be related to the crystalline nature of the carrier matrix in combination wit h its colloidal state. Observation of the supercooling effect has led to th e development of a second new type of carrier system: nanospheres of superc ooled melts. This novel type of colloidal lipidic carrier represents an int ermediate state between emulsions and suspensions. Moreover, these dispersi ons are particularly suited to the study of the basic differences between c olloidal triglyceride emulsions and suspensions. For many decades drug carr iers have represented the only group of colloidal drug administration syste ms. Nowadays a fundamentally different group of dispersions is also under i nvestigation: drug nanodispersions. They overcome a number of carrier-relat ed drawbacks, such as limitations in drug load as well as side effects due to the matrix material of the carrier particles. Utilizing this concept vir tually insoluble drugs can be formulated as colloidal particles, of solid o r supercooled nature. For example, coenzyme Q(10) (Q(10)) has been successf ully processed into a dispersion of a supercooled melt. Droplet sizes in th e lower nanometer range and shelf lives of more than 3 years can easily be achieved for Q(10) dispersions. The drug load of the emulsion particles rea ches nearly 100%.