Drug nanoparticles embedded in a dispersant matrix as a secondary phase, i.e., drug-laden nanocomposites, offer a versatile delivery platform for enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Drug nanoparticles are prepared by top-down, bottom-up, or combinative approaches in the form of nanosuspensions, which are subsequently dried to prepare drug-laden nanocomposites. In this comprehensive review paper, the term “nanocomposites” is used in a broad context to cover drug nanoparticle-laden intermediate products in the form of powders, cakes, and extrudates, which can be incorporated into final oral solid dosages via standard pharmaceutical unit operations, as well as drug nanoparticle-laden strip films. The objective of this paper is to review studies from 2012–2017 in the field of drug-laden nanocomposites. After a brief overview of the various approaches used for preparing drug nanoparticles, the review covers drying processes and dispersant formulations used for the production of drug-laden nanocomposites, as well as various characterization methods including quiescent and agitated redispersion tests. Traditional dispersants such as soluble polymers, surfactants, other water-soluble dispersants, and water-insoluble dispersants, as well as novel dispersants such as wet-milled superdisintegrants, are covered. They exhibit various functionalities such as drug nanoparticle stabilization, mitigation of aggregation, formation of nanocomposite matrix–film, wettability enhancement, and matrix erosion/disintegration. Major challenges such as nanoparticle aggregation and poor redispersibility that cause inferior dissolution performance of the drug-laden nanocomposites are highlighted. Literature data are analyzed in terms of usage frequency of various drying processes and dispersant classes. We provide some engineering considerations in comparing drying processes, which could account for some of the diverging trends in academia vs. industrial practice. Overall, this review provides rationale and guidance for drying process selection and robust nanocomposite formulation development, with insights into the roles of various classes of dispersants.

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 aimed to examine the impact of milling of extrudates prepared via nanoextrusion and the resulting matrix surface area of the particles on griseofulvin (GF, a model poorly soluble drug) release during in vitro dissolution. Wet-milled GF nanosuspensions containing a polymer (Sol: Soluplus^®, Kol: Kolliphor^® P407, or HPC: Hydroxypropyl cellulose) and sodium dodecyl sulfate were mixed with additional polymer and dried in an extruder. The extrudates with 2% and 10% GF loading were milled–sieved into three size fractions. XRPD–SEM results show that nanoextrusion produced GF nanocomposites with Kol/HPC and an amorphous solid dispersion (ASD) with Sol. For 8.9 mg GF dose (non-supersaturating condition), the dissolution rate parameter was higher for extrudates with higher external specific surface area and those with 10% drug loading. It exhibited a monotonic increase with surface area of the ASD, whereas its increase tended to saturate above ~30 × 10⁻³ m²/cm³ for the nanocomposites. In general, the nanocomposites released GF faster than the ASD due to greater wettability and faster erosion imparted by Kol/HPC than by Sol. For 100 mg GF dose, the ASD outperformed the nanocomposites due to supersaturation and only 10% GF ASD with 190 × 10⁻³ m²/cm³ surface area achieved immediate release (80% release within 30 min). Hence, this study suggests that ASD extrudates entail fine milling yielding > ~200 × 10⁻³ m²/cm³ for rapid drug release, whereas only a coarse milling yielding ~30 × 10⁻³ m²/cm³ may enable nanocomposites to release low-dose drugs rapidly.