Malamatari Maria, Somavarapu Satyanarayana, Taylor Kevin M G, Buckton Graham
a Department of Pharmaceutics , UCL School of Pharmacy , London , UK.
Expert Opin Drug Deliv. 2016;13(3):435-50. doi: 10.1517/17425247.2016.1142524. Epub 2016 Feb 3.
Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of nanosuspensions to solid oral and inhalable dosage forms minimises the physical instability associated with their liquid state, enhances patient compliance and enables targeted oral and pulmonary drug delivery.
This review outlines solidification methods for nanosuspensions. It includes spray and freeze drying as the most widely used techniques. Fluidised-bed coating, granulation and pelletisation are also discussed as they yield nanocrystalline formulations with more straightforward downstream processing to tablets or capsules. Spray-freeze drying, aerosol flow reactor and printing of nanosuspensions are also presented as promising alternative solidification techniques. Results regarding the solid state, in vitro dissolution and/or aerosolisation efficiency of the nanocrystalline formulations are given and combined with available in vivo data. Focus is placed on the redispersibility of the solid nanocrystalline formulations, which is a prerequisite for their clinical application.
A few solidified nanocrystalline products are already on the market and many more are in development. Oral and inhalable nanoparticle formulations are expected to have great potential especially in the areas of personalised medicine and delivery of high drug doses (e.g. antibiotics) to the lungs, respectively.
纳米混悬液兼具纳米治疗药物的优势(如提高溶解速率和饱和溶解度)以及易于商业化的特点。将纳米混悬液转化为固体口服和吸入剂型可最大程度减少与其液态相关的物理不稳定性,提高患者顺应性,并实现靶向口服和肺部给药。
本综述概述了纳米混悬液的固化方法。其中包括喷雾干燥和冷冻干燥这两种最广泛使用的技术。还讨论了流化床包衣、制粒和造粒,因为它们可生产出纳米晶体制剂,其后续加工成片剂或胶囊更为直接。喷雾冷冻干燥、气溶胶流动反应器和纳米混悬液打印也作为有前景的替代固化技术被提及。给出了纳米晶体制剂的固态、体外溶出和/或雾化效率的相关结果,并与现有的体内数据相结合。重点关注固体纳米晶体制剂的再分散性,这是其临床应用的前提条件。
一些固化的纳米晶体产品已上市,还有更多产品正在研发中。口服和吸入纳米颗粒制剂预计分别在个性化医疗和向肺部递送高剂量药物(如抗生素)等领域具有巨大潜力。