(306f) Engineered Particles Prepared Via Drying of Drug Nanosuspensions for Bioavailability Enhancement

Drug nanosuspensions of poorly water soluble drugs were prepared by wet stirred media milling in the Netzsch mill. Different polymers and surfactants were used to prevent the aggregation of these nanoparticles via adsorption of the stabilizers on the nanoparticle surfaces. The nanosuspensions were converted into powders by coating of these nanosuspensions on inert beads (Celphere) in a fluid bed coater for solid oral dosage forms. The redispersion of nanosuspensions after drying lead to increase in the particle size of drug nanoparticles as the stabilizers lose their functionality during the drying process. Therefore, the bioavailability improvement expected from nanoparticles was not realized. Hence the formulation and coating process parameters will be explored in this study as they affect the particle attributes leading to poor redispersibility. The preliminary results of the addition of matrix formers lactose, sucrose and mannitol in the formulation of nanosuspensions before coating to recover the original drug nanoparticles will be presented. The role of matrix formers, concentration of matrix formers required for redispersibility and effect of method of addition of matrix formers before or after milling of poorly soluble drugs will be discussed. This study will also shed some light on the process parameters of the fluid bed coating process to obtain uniform coating of the inert beads to ensure drug content uniformity. The crystalline/amorphous nature of the drugs after processing, drug content uniformity, particle size and flowability of these engineered particles will also be investigated.