Particle Size Reduction Techniques of Pharmaceutical Compounds for the Enhancement of Their Dissolution Rate and Bioavailability

In pharmaceutical research and development, various new chemical entities (NCE) are found to be poorly water-soluble. Therefore, solubility enhancement, a key factor for higher bioavailability, is a major challenge in pharmaceutical industries. Particle size reduction is one such method that increases the surface area of the pharmaceutical compounds and subsequently leads to a higher dissolution rate and bioavailability. Conventional processes such as milling, high-pressure homogenization, and spray drying are well established and widely used for particle size reduction. However, a few disadvantages such as a broader particle size distribution (PSD) and thermal and chemical degradation of the product are major concerns for the product quality. Non-conventional processes such as liquid anti-solvent crystallization, supercritical anti-solvent process, rapid expansion of supercritical solutions, particles from gas saturated solutions, and pulsed laser ablation are emerging as potential alternatives to overcome the disadvantages of conventional processes. This review critically summarizes the milling, spray drying, high-pressure homogenization, liquid anti-solvent crystallization, spray freeze-drying, supercritical carbon dioxide (SC CO2)-based micronization processes, pulsed laser ablation and combinative techniques. The success of these processes in enhancing the dissolution rate and bioavailability of many active pharmaceutical ingredients (APIs) has been critically examined. The advantages and limitations of these processes are also discussed. Finally, opportunities for future research are also proposed.

Automated summary

The article summarizes various methods for reducing the particle size of pharmaceuticals and their advantages and limitations, and proposes non-traditional processes as potential alternatives to overcome the disadvantages of traditional processes.