Schoenitz M, Joseph S, Nitz A, Bunjes H, Scholl S
Technische Universität Braunschweig, Institute for Chemical and Thermal Process Engineering (ICTV), Braunschweig, Germany.
Technische Universität Braunschweig, Institute for Pharmaceutical Technology, Braunschweig, Germany.
Eur J Pharm Biopharm. 2014 Apr;86(3):324-31. doi: 10.1016/j.ejpb.2013.08.009. Epub 2013 Aug 20.
The contribution describes the transfer from a batch to a micro-continuous process for the production of stable solid lipid nanoparticles as drug carrier systems. Solid lipid nanoparticles are commonly prepared batch-wise often resulting in poorly defined product qualities with regard to the polymorphic state of their lipid matrix. In order to obtain solid lipid nanoparticle dispersions that meet the requirements for an acceptable pharmaceutical product, the manufacture of reproducible product qualities preferably containing the stable crystal form of the respective matrix lipid is necessary. These requests are addressed by the continuous preparation process of solid lipid nanoparticles. A four step feasibility study for the standardized evaluation whether or not a colloidal lipid dispersion is suitable for continuous crystallization of the particles resulting in stable crystal forms is presented. The process is based on the continuous crystallization and subsequent thermal treatment of differently stabilized, tripalmitin-based nanoparticle formulations in microstructured devices. The successful production of the stable crystal form by means of a continuous process chain is shown for a dispersion stabilized with a blend of hydrogenated soybean lecithin and sodium glycocholate.
本论文介绍了从间歇式生产向微连续化生产转变，用于制备作为药物载体系统的稳定固体脂质纳米粒。固体脂质纳米粒通常采用间歇式制备，这常常导致其脂质基质的多晶型状态下产品质量难以明确界定。为了获得符合可接受药品要求的固体脂质纳米粒分散体，制造具有可重现产品质量、优选包含相应基质脂质稳定晶型的产品是必要的。固体脂质纳米粒的连续制备工艺解决了这些要求。本文提出了一个四步可行性研究，用于标准化评估胶体脂质分散体是否适合颗粒的连续结晶以产生稳定晶型。该工艺基于在微结构装置中对不同稳定化的、基于三棕榈酸甘油酯的纳米粒制剂进行连续结晶和后续热处理。对于用氢化大豆卵磷脂和甘氨胆酸钠混合物稳定的分散体，展示了通过连续工艺链成功生产稳定晶型的过程。
