This study aimed to elucidate the impact of a common anionic surfactant, sodium dodecyl sulfate (SDS), along with hydroxypropyl cellulose (HPC) and Soluplus (Sol) on the release of griseofulvin (GF), a poorly soluble drug, from amorphous solid dispersions (ASDs). Solutions of 2.5% GF and 2.5%–12.5% HPC/Sol with 0.125% SDS/without SDS were prepared in acetone–water and spray-dried. The solid-state characterization of the ASDs suggests that GF–Sol had better miscibility and stronger interactions than GF–HPC and formed XRPD-amorphous GF, whereas HPC-based ASDs, especially the ones with a lower HPC loading, had crystalline GF. The dissolution tests show that without SDS, ASDs provided limited GF supersaturation (max. 250%) due to poor wettability of Sol-based ASDs and extensive GF recrystallization in HPC-based ASDs (max. 50%). Sol-based ASDs with SDS exhibited a dramatic increase in supersaturation (max. 570%), especially at a higher Sol loading, whereas HPC-based ASDs with SDS did not. SDS did not interfere with Sol’s ability to inhibit GF recrystallization, as confirmed by the precipitation from the supersaturated state and PLM imaging. The favorable use of SDS in a ternary ASD was attributed to both the wettability enhancement and its inability to promote GF recrystallization when used as a minor component along with Sol.

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 (~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.

Dry coating fine pharmaceutical powders with nano-silica has been shown to enhance their bulk properties and their blend processability at lab-scale, potentially facilitating tablet manufacturing. This study critically investigates key aspects of dry coating from industrial applicability perspective: (1) evaluating the selection of silica amount based on the host particle surface area coverage (SAC) against the industry standard 1 wt% addition, (2) assessing the feasibility of continuous dry coating using a pilot-scale conical screen mill (comil-U10) compared to the lab-scale batch high-intensity vibratory mixer (HIVM), and (3) investigating downstream processing improvements from dry coating via feedability and tabletability studies. Results from six different pharmaceutical powders (d50 ∼ 3-35 μm) demonstrated that SAC-based silica wt.% selection outperformed 1 wt% silica for bulk properties enhancements. Multi-faceted characterization revealed that FFC was the most reliable amongst Hausner's ratio, compressibility, and permeability tests. Three selected materials (d50 ∼ 16-26 μm) for comil processing showed remarkable one-flow category improvement, though two finer materials fell short of the HIVM performance. The dry coated materials demonstrated superior feed rate stability, demonstrating reduced flow variability, attributed to enhanced flowability and lower compressibility. Tablets of formulations containing dry-coated API using either comil or HIVM outperformed formulations with blended silica at three drug loads, 10 %, 30 %, and 60 %, likely due to better silica dispersion. These outcomes demonstrate the benefits of potentially scalable comil-based dry coating to continuous manufacturing of tableting, potentially eliminating the need for granulation.