Insights to the action of additives for stabilization of ultrafine particles of Fenofibrate in aqueous suspensions produced by Sonoprecipitation

Sonoprecipitation of Fenofibrate (FNB) was carried out in the presence of polymeric additives and surfactants. The particle size and morphology was found to be significantly affected by the mixing conditions and the type of additives used. In order to understand the mechanism by which the additives affect FNB particle growth and morphology, intermolecular interactions between the additive and FNB crystal surfaces were modeled. Among the additives used, Tween 80 was found to be a great habit modifier. Hydrogen bonding interactions between Tween 80 and FNB molecules exposed on the (010) face of FNB particles leads to a needle-like morphology. The experimental and modelling studies indicate that hydroxyl propyl methyl cellulose (HPMC) and bovine serum albumin (BSA) show stronger crystal growth inhibition effect and provide better stabilization compared to polyvinyl pyrolidone (PVP) and Tween 80. FNB particles precipitated with ultrasound and additives were found to exhibit faster drug release profiles compared to the particles precipitated without ultrasound but in the presence of additives.