Keck Cornelia M, Müller Rainer H
PharmaSol GmbH, Berlin, Germany.
Eur J Pharm Biopharm. 2006 Jan;62(1):3-16. doi: 10.1016/j.ejpb.2005.05.009. Epub 2005 Aug 29.
For many new chemical entities (NCE) of very low solubility oral bioavailability enhancement by micronisation is not sufficient, the next step taken was nanonisation. The production of drug nanocrystals by bottom up techniques (precipitation) is briefly described, main focus is given on particle diminution by high pressure homogenisation. Homogenisation can be performed in water (DissoCubes) or alternatively in non-aqueous media or water-reduced media (Nanopure). There is also a combination process of precipitation followed by a second high energy step, e.g. homogenisation (NANOEDGE). The result is a suspension of drug nanocrystals in a liquid, the so-called nanosuspension. Presented are the physical background of the diminution process, effects of production parameters (power density, number of homogenisation cycles) on crystal size, clinical batch production and scaling up of the production. As an important point the transfer of the liquid nanosuspensions to patient convenient oral dosage forms such as tablets and capsules is described.
对于许多溶解度极低的新化学实体（NCE）而言，通过微粉化提高口服生物利用度并不足够，接下来采取的步骤是纳米化。简要描述了通过自下而上技术（沉淀法）制备药物纳米晶体的过程，重点介绍了通过高压均质化减小颗粒尺寸的方法。均质化可以在水中（DissoCubes）进行，也可以在非水介质或低水介质（Nanopure）中进行。还有一种沉淀法结合第二步高能步骤（如均质化）的联合工艺（NANOEDGE）。其结果是在液体中形成药物纳米晶体的悬浮液，即所谓的纳米混悬液。介绍了减小颗粒尺寸过程的物理背景、生产参数（功率密度、均质化循环次数）对晶体尺寸的影响、临床批次生产以及生产规模扩大的情况。作为一个重点内容，还描述了将液体纳米混悬液转化为患者方便使用的口服剂型（如片剂和胶囊）的过程。
