Tailoring Particle Microstructures via Supercritical CO₂ Processes for Particular Drug Delivery

Strategies for a particular drug delivery are always of great interest to the pharmaceutical industry, and efficient methods of preparing products with controlled particle microstructures are fundamental for the development and application of drug delivery. Supercritical fluid particle design (SCF PD) processes, as a green and effective alternative to traditional methods, have been effectively employed to produce particles with designated microstructures. Combining with research experiences in our research group, this review aims to provide a roadmap of SCF PD for particular drug delivery. For any drug delivery formulations, macroscopic properties (administration methods, drug release behaviour and targeting) are directly influenced by the particle microstructures (morphology, particle size, particle size distribution, crystal form, drug loading, encapsulation efficiency, etc). "Inverse" strategies are introduced at first to obtain the necessary particle microstructures for a particular drug delivery in this paper. Then, how to produce particles with designated microstructures via SCF PD processes is discussed, mainly focusing on the screening and selection of operating parameters according to thermodynamic and fluid dynamic studies. Recent examples of SCF micronization and co-precipitation/encapsulation processes are also summarized with an emphasis on how to tailor the particle microstructures by controlling the operating parameters. Finally, challenges and issues needing further study are briefly suggested for SCD PD.