Determination of surface-adsorbed excipients of various types on drug particles prepared by antisolvent precipitation using HPLC with evaporative light scattering detection

A common challenge in the development of new drug substances is poor dissolution characteristics related to low aqueous solubility. One approach to overcome this problem is antisolvent precipitation in the presence of polymers or surfactants, which may enhance the dissolution rate through reduced particle size and increased wettability. In this study, a simple method based on size exclusion chromatography (SEC) with evaporative light scattering detection (ELSD) was developed for the determination of polymers and surfactants adsorbed to drug particles prepared by antisolvent precipitation of the poorly water-soluble model drug Lu 28–179. Detection of many polymeric excipients and surfactants is problematic due to the lack of UV-absorbing chromophores, but ELSD proved successful for the direct determination of the investigated compounds. A mixed mode column was used to effectively separate each of the excipient structures from the drug. The mobile phase comprised acetonitrile–ammonium formate (20 mM; pH 6.5) (50:50, v/v) at a flow-rate of 0.6 ml/min. Qualification studies showed that the method was adequately sensitive and precise with limits of detection between 0.72 and 4.32 μg/ml. Linearity of the calibration curves was achieved by log–log modelling. The method was applied for determination of nine polymeric excipients and surfactants adsorbed to particles of the model drug. The extent of excipient adsorption varied between 0.07 and 1.39% (w/w) of the total particle weight.