Nanosuspension

Nanosuspension is a submicron colloidal dispersion in which solid drug particles are dispersed in a liquid medium, stabilized by surfactants or polymers. The solid phase consists of nanocrystals with typical particle sizes ranging from about 10 to 1000 nanometers. Nanosuspensions are primarily used to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs, but they can also be formulated for parenteral, ocular, topical, and transdermal routes.

Stabilization and particle size control are achieved through top-down or bottom-up approaches. Top-down methods include milling and high-pressure homogenization that reduce particle size in the presence of stabilizers. Bottom-up methods rely on precipitation or controlled crystallization of the drug from solution, often followed by stabilization. Hybrid approaches that combine elements of both strategies are common. Stabilizers, such as polymers, hydrogen-bond donors, and small-molecule surfactants (for example poloxamers, Tween, Span), prevent aggregation. Stabilization mechanisms are primarily steric, electrostatic, or electrosteric, and are selected to achieve a suitable zeta potential and long-term stability.

Advantages include enhanced dissolution rate, increased saturation solubility, and potential for higher bioavailability, enabling dose form flexibility and applicability to multiple administration routes, including injectable suspensions for hydrophobic drugs. Limitations involve physical instability (Ostwald ripening and aggregation), sensitivity to storage conditions, potential solvent residues, challenges in scale-up, and sterilization considerations for injectables.

Characterization of nanosuspensions involves particle size and distribution by dynamic light scattering, zeta potential measurement, electron microscopy for morphology, crystallinity assessment by DSC or XRD, drug content analysis, and in vitro dissolution testing. Regulatory considerations focus on stability, compatibility with excipients, and process validation in the context of specific routes of administration.