Department of Chemical and Biological Engineering, Princeton University, NJ 08544, USA.
Adv Drug Deliv Rev. 2011 May 30;63(6):417-26. doi: 10.1016/j.addr.2011.04.005. Epub 2011 Apr 30.
Nanoparticles are a drug delivery platform that can enhance the efficacy of active pharmaceutical ingredients, including poorly-water soluble compounds, ionic drugs, proteins, peptides, siRNA and DNA therapeutics. To realize the potential of these nano-sized carriers, manufacturing processes must be capable of providing reproducible, scalable and stable formulations. Antisolvent precipitation to form drug nanoparticles has been demonstrated as one such robust and scalable process. This review discusses the nucleation and growth of organic nanoparticles at high supersaturation. We present process considerations for controlling supersaturations as well as physical and chemical routes for modifying API solubility to optimize supersaturation and control particle size. We conclude with a discussion of post-precipitation factors which influence nanoparticle stability and efficacy in vivo and techniques for stabilization.
纳米粒子是一种药物传递平台，可增强活性药物成分的功效，包括水溶性差的化合物、离子药物、蛋白质、肽、siRNA 和 DNA 治疗剂。为了实现这些纳米载体的潜力，制造工艺必须能够提供可重复、可扩展和稳定的配方。抗溶剂沉淀法形成药物纳米粒子已被证明是一种强大且可扩展的工艺。本文讨论了在高过饱和度下有机纳米粒子的成核和生长。我们提出了控制过饱和度的工艺考虑因素，以及物理和化学途径来改变 API 的溶解度，以优化过饱和度并控制粒径。最后，我们讨论了影响体内纳米粒子稳定性和功效的沉淀后因素以及稳定技术。
