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 \((\mathrm{SC C}{\mathrm{O}}_{2})\)–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.

在药物研究和开发中，发现各种新的化学实体（NCE）水溶性差。因此，增加溶解度是提高生物利用度的关键因素，是制药行业的主要挑战。减小粒径是一种增加药物化合物表面积并随后导致更高的溶解速率和生物利用度的方法。诸如碾磨，高压均质化和喷雾干燥之类的常规方法已被很好地建立并且广泛用于减小粒度。但是，一些缺点，例如较宽的粒度分布（PSD）以及产品的热降解和化学降解是产品质量的主要问题。非常规过程，例如液体反溶剂结晶，超临界反溶剂工艺，超临界溶液的快速膨胀，气体饱和溶液中的颗粒以及脉冲激光烧蚀正在成为克服常规工艺缺点的潜在替代方法。该评论批判性地总结了研磨，喷雾干燥，高压均质化，液体反溶剂结晶，喷雾冷冻干燥，超临界二氧化碳\（（\ mathrm {SC C} {\ mathrm {O}} _ {2}）\）–基于微粉化工艺，脉冲激光烧蚀和组合技术。严格审查了这些方法在提高许多活性药物成分（API）的溶出速率和生物利用度方面的成功。还讨论了这些过程的优点和局限性。最后，还提出了未来研究的机会。