(645a) Hybrid Nanocrystal-Amorphous Solid Dispersions (HyNASDs): A New Class of Materials for Bioavailability Enhancement of Poorly Soluble Drugs

Drug nanoparticle-laden microparticles (nanocomposites) and amorphous solid dispersions (ASDs) have been commonly used to deliver poorly soluble drugs and enhance their solubility, dissolution rate, and bioavailability. A major shortcoming of drug nanocomposites as compared with drug ASDs is their limited supersaturation capability in dissolution, whereas ASDs have various issues about physical stability of the metastable form of the drug (amorphous). Here, we prepared drug hybrid nanocrystal–amorphous solid dispersions (HyNASDs) and compared their performance to ASDs. A wet-milled griseofulvin (GF, model poorly soluble drug) nanosuspension and a GF solution, both containing the same dissolved polymer–surfactant (SDS: sodium dodecyl sulfate) with 1:1, 1:3, and 1:5 GF:polymer mass ratios, were spray-dried. Hydroxypropyl cellulose (HPC) and Soluplus (Sol) were used as matrix-forming polymers. XRPD, DSC, and Raman spectroscopy reveal that ASDs were formed upon spray-drying the solution-based feed, whereas nanocomposites and nanocomposites with >10% amorphous content, HyNASDs, were formed with the nanosuspension-based feed. Sol provided higher GF relative supersaturation in the dissolution tests than HPC owing to Sol’s stronger intermolecular interactions and miscibility with GF and its recrystallization inhibition. Besides the higher kinetic solubility of GF in Sol, presence of GF nanoparticles vs. micron-sized particles in the nanocomposites enabled fast supersaturation. SDS provided enhanced wettability, allowing for fast supersaturation from Soluplus-based HyNASDs (~300% within 20 min), while higher Soluplus loading led to higher supersaturation. This study demonstrates successful preparation of fast supersaturating HyNASDs, which renders nanoparticle formulations competitive to ASDs in bioavailability enhancement of poorly soluble drugs.