Katrin Peters

Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique

Abstract A basic problem of poorly soluble drugs is often an insufficient bioavailability. To allow the i.v. injection of these drugs, they were formulated as nanosuspensions by high pressure homogenization. The effect of the production parameters pressure and cycle number on the mean particle size and on the polydispersity of the nanosuspension was investigated with special attention to contamination by microparticles — the limiting factor for i.v. injection. Properties of the nanosuspensions are increased saturation solubility C s and dissolution rate d c /d t . These phenomena are explained using the Prandtl and the Ostwald–Freundlich equations. These properties promote the dissolution of the nanosuspensions in the blood after i.v. injection. The size distribution obtained and the use of an APV Gaulin homogenizer (FDA approved for parenterals) lead to a pharmaceutical product considered acceptable by the regulatory authorities.

An investigation into the distribution of lecithins in nanosuspension systems using low frequency dielectric spectroscopy

A range of nanosuspensions comprising a model drug (RMKP 22) with varying concentrations of Phospholipon 90 were prepared using high pressure homogenization and analyzed using low frequency dielectric spectroscopy as a novel means of characterizing the distribution of Phospholipon 90 within the suspensions. A corresponding range of aqueous Phospholipon 90 suspensions were also studied for the purpose of comparison. The dielectric responses were interpreted using a modification of the Maxwell-Wagner approach, whereby the systems were considered to comprise a high frequency response corresponding to the bulk layer serially connected to a lower frequency response corresponding to an electrode barrier layer. The low frequency responses of both the Phospholipon 90 dispersions and the nanosuspensions were found to be essentially independent of phospholipid concentration, indicating the presence of a barrier layer covering the electrode surfaces. In contrast, the high frequency (bulk) loss response was found to increase with Phospholipon 90 concentration for the surfactant suspensions while a maximum in response was seen with Phospholipon 90 concentration for the nanosuspensions; this behaviour was attributed to the presence of impurities within the phospholipids. Based on this investigation, a model is proposed with which the dielectric response may be related to the surface coverage of the suspended drug particles.