Moll Fabian, Bechtold-Peters Karoline, Mellman James, Sigg Jurgen, Friess Wolfgang
Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University Munich, Germany.
Technical Research and Development (TRD) Biologics, Novartis Pharma AG, Basel, Switzerland.
PDA J Pharm Sci Technol. 2021 Aug 16. doi: 10.5731/pdajpst.2021.012640.
Pre-filled syringes have simplified parenteral administration of protein drugs. To ensure an easy and consistent movement of the plunger, the inner glass container surface is typically siliconized. For bake-on siliconization emulsions are sprayed on and heat treated. Due to the European Union regulation REACh (Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals) the use of certain emulsion components, partially constituting the gold standard Liveo™ 365 35% Dimethicone NF Emulsion (Liveo™ 365), becomes restricted and Liveo™ 366 35% Dimethicone NF Emulsion (Liveo™ 366) has been introduced as an alternative. This change may affect the handling properties as well as the silicone layer formed. The purpose of these studies was to identify any differences that may influence the stability and safety of the final drug/device combination product to enable the use of the new emulsion. We compared silicone emulsions Liveo™ 365 and Liveo™ 366 and dilutions focusing on I) their general physical stability, II) the thermal degradation process of the emulsions and their components, and III) the resulting silicone layer concerning chemistry, morphology, and functionality. The results were linked to the assessment of the final product regarding particle formation and long-term stability. A comparison of the emulsions Liveo™ 365 and Liveo™ 366 for bake-on siliconization is presented to support the transition of the latter as it becomes mandatory with REACh. Our studies show that the two emulsions do not significantly differ with respect to handling and stability, the resultant silicone layer characteristics as well as its functionality. We conclude that the transition to the new emulsion will not significantly impact the final product or the layer performance upon storage and with respect to particle formation.
预填充注射器简化了蛋白质药物的肠胃外给药。为确保柱塞轻松且一致地移动，内部玻璃容器表面通常会进行硅化处理。对于烘焙硅化，会将乳液喷涂并进行热处理。由于欧盟化学品注册、评估、授权和限制法规（REACh），某些构成金标准的Liveo™ 365 35%二甲基硅油NF乳液（Liveo™ 365）的乳液成分的使用受到限制，Liveo™ 366 35%二甲基硅油NF乳液（Liveo™ 366）已作为替代品推出。这一变化可能会影响操作性能以及形成的硅氧烷层。这些研究的目的是确定可能影响最终药物/器械组合产品稳定性和安全性的任何差异，以便能够使用新的乳液。我们比较了Liveo™ 365和Liveo™ 366硅氧烷乳液及其稀释液，重点关注：I）它们的一般物理稳定性；II）乳液及其成分的热降解过程；III）所得硅氧烷层的化学、形态和功能。结果与最终产品在颗粒形成和长期稳定性方面的评估相关联。本文对Liveo™ 365和Liveo™ 366乳液用于烘焙硅化进行了比较，以支持后者的过渡，因为随着REACh法规的实施，这一过渡变得必不可少。我们的研究表明，这两种乳液在操作和稳定性、所得硅氧烷层特性及其功能方面没有显著差异。我们得出结论，向新乳液的过渡不会对最终产品或储存时以及颗粒形成方面的层性能产生显著影响。
