Nanocrystal Formulation Strategies for Drug Delivery

Nanocrystals are submicron crystalline drug particles engineered to enhance solubility, dissolution rate and bioavailability of poorly water-soluble compounds. Formulation strategies broadly fall into top-down and bottom-up approaches. Top-down methods such as wet media milling and high-pressure homogenisation reduce bulk drug to nanoscale, while bottom-up methods rely on controlled precipitation or anti-solvent addition to assemble nanocrystals from molecular solutions. Stabilisation by minimal surfactants or polymers is critical to prevent aggregation, control surface properties and tailor release kinetics. Quality-by-Design (QbD) principles and Design of Experiments (DoE) frameworks are increasingly applied to define critical process parameters and design space, enabling robust scale-up and reproducible control of particle size distribution and polydispersity. Characterisation techniques including dynamic light scattering, electron microscopy and solid-state analysis inform stability, crystallinity and redispersibility. Nanocrystals have been deployed across oral, parenteral, pulmonary and topical routes, with emerging applications in targeted delivery and combination therapies. Regulatory approval of several nanocrystal-based medicines highlights clinical translation, while ongoing work addresses long-term stability, safety of excipients and controlled release design for precision dosing.

Research from Nature Portfolio

Studies investigating nanocrystal formulations of atorvastatin have demonstrated how high-pressure homogenisation combined with lyophilisation and optimised stabiliser selection can yield uniform nanocrystals (~225 nm) with reduced crystallinity and improved dispersibility. Poloxamer-188 was tuned with drug ratio, homogenisation cycles and cryoprotectant type to achieve fourfold enhancement in gastric solubility and a 2.6-fold increase in oral bioavailability in preclinical models. These nanocrystals also achieved superior lipid-lowering efficacy at half the conventional dose, underscoring safety gains and scalable production potential for hyperlipidaemia treatment.

Nanocrystal Formulation Strategies for Drug Delivery publication trend

The graph below shows the total number of articles in nanocrystal formulation strategies for drug delivery across all publications each year (not limited to Nature Index journals).

Technical terms

Nanocrystal: Pure drug particles reduced to nanometre dimensions, stabilised by minimal excipients to enhance dissolution and bioavailability.

Top-down approach: Technique where bulk drug is milled or homogenised to break particles down to nanoscale.

Bottom-up approach: Method in which drug molecules self-assemble into nanocrystals via controlled precipitation or anti-solvent addition.

Polydispersity index (PdI): Quantitative measure of particle size distribution; values below 0.3 indicate a uniform nanoscale population.

Quality by Design (QbD): Systematic development approach that defines Critical Quality Attributes and Critical Process Parameters to ensure consistent product quality.

References

1. Step‐By‐Step Standardization of the Bottom‐Up Semi‐Automated Nanocrystallization of Pharmaceuticals: A Quality By Design and Design of Experiments Joint Approach. Small (2024).
2. Recent developments in the use of nanocrystals to improve bioavailability of APIs. Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology (2024).
3. Progress in the development of stabilization strategies for nanocrystal preparations. Drug Delivery (2020).
4. Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential. Scientific Reports (2019).