Preparation and Characterization of Spray-Dried Hybrid Nanocrystal-Amorphous Solid Dispersions (HyNASDs) for Supersaturation Enhancement of a Slowly Crystallizing Drug

We prepared hybrid nanocrystal-amorphous solid dispersions (HyNASDs) to examine their supersaturation capability in the release of a poorly soluble drug, itraconazole (ITZ), a slow crystallizer during dissolution. The HyNASD formulations included a polymer (HPC: hydroxypropyl cellulose, Sol: Soluplus, or VA64: Kollidon-VA64) and a surfactant (SDS: sodium dodecyl sulfate). Additionally, the dissolution performance of the HyNASDs and ASDs was compared. To this end, wet-milled aqueous nanosuspensions containing a 1:5 ITZ:polymer mass ratio with/without SDS as well as solutions of the same ratio without SDS in dichloromethane were spray-dried. XRPD-DSC confirmed that ASDs were formed upon spray drying the solution-based feeds, whereas HyNASDs (similar to 5-30% amorphous) were formed with the nanosuspension-based feeds. SDS aided to stabilize the ITZ nanosuspensions and increase the amorphous content in the spray-dried powders. During dissolution, up to 850% and 790% relative supersaturation values were attained by HyNASDs with and without SDS, respectively. Due to the stronger molecular interaction between ITZ-Sol than ITZ-HPC/VA64 and micellar solubilization by Sol, Sol-based HyNASDs outperformed HPC/VA64-based HyNASDs. While the ASD formulations generated greater supersaturation values (<= 1670%) than HyNASDs (<= 790%), this extent of supersaturation from a largely nanocrystalline formulation (HyNASD) has not been achieved before. Overall, HyNASDs could boost drug release from nanoparticle-based formulations and may render them competitive to ASDs.

Automated summary

In this study, hybrid nanocrystal-amorphous solid dispersions (HyNASDs) were prepared to enhance the dissolution rate of the poorly soluble drug itraconazole. The addition of a surfactant, SDS, aided in stabilizing the nanosuspensions and increasing the amorphous content. HyNASDs achieved supersaturation values of up to 850% and 790% during dissolution, surpassing the performance of ASDs and traditional nanoparticle-based formulations.