Nanosuspensions and Solutions for Preparation of Nanocomposites and Amorphous Solid Dispersions: Comparative Assessment of Drug Release

The number of poorly water-soluble drug candidates coming out of drug discovery has increased over the past decades. The low water solubility of these drugs poses a great challenge since it is frequently the rate-limiting step in the intestinal drug absorption which negatively affect bioavailability. Two major platform approaches which improve the dissolution rate and bioavailability of poorly water-soluble drugs are the nanomilling of a drug suspension followed by drying (nanocomposites) for higher surface area or formation of an amorphous solid dispersion (ASD) for higher saturation solubility. Here, we aim to assess the dissolution enhancement of griseofulvin (GF, a poorly water-soluble drug) from nanocomposites vs. ASDs, both having identical formulations. GF nanocomposite was prepared by wet media milling (nanomilling) of an aqueous GF suspension followed by spray drying. Two different polymers, hydroxypropyl cellulose (HPC) and Soluplus®, with an anionic surfactant, sodium dodecyl sulfate (SDS), were used for the stabilization of drug nanoparticles. ASDs were prepared by spray-drying a solution of the respective drug–polymer ratio in acetone-DI water. The suspensions were characterized via laser diffraction, while the spray-dried powders were characterized using laser diffraction, X-ray diffraction (XRD), Scanning electron microscopy (SEM), and dissolution testing. XRD diffractograms confirmed that for both polymers, spray-drying of the aqueous nanosuspension led to drug nanocrystals in the polymeric matrix (nanocomposite), whereas that of the drug solution led to ASD. Dissolution testing at supersaturating conditions showed faster drug release and higher extent of supersaturation from ASD than from nanocomposites in case of Soluplus® but showed similar performance in case of HPC.