Eli Lilly & Company, Pharmaceutical Engineering Technology Center, Lilly Technology Center, 1555 S. Harding Street, Indianapolis, IN 46221; and
Eli Lilly & Company, Pharmaceutical Engineering Technology Center, Lilly Technology Center, 1555 S. Harding Street, Indianapolis, IN 46221; and.
PDA J Pharm Sci Technol. 2020 Jan-Feb;74(1):73-89. doi: 10.5731/pdajpst.2018.009431. Epub 2019 Aug 16.
A model was developed that can be used to predict how hydrogen peroxide (HO) transfers into a liquid drug product that is exposed to vapor phase hydrogen peroxide (VPHP). This model accounts for fluid flow in both the gas and liquid phases as well as the diffusion and convection mechanisms of mass transfer using the first principles of engineering to predict the amount of HO that will transfer from the gas to the liquid phase considering a given geometrical system and surrounding conditions. The model was used to investigate how much space is needed in a given container to eliminate convective mass transfer and to create a balance between mass transfer and the air/liquid interface for oxidation-sensitive products in cartridges or vials being filled in an isolator. Experimental results compared well with model predictions. A no-slip boundary condition between the gas and liquid phases was used for the model, which was especially important for the full syringes where convective mass transport predominated. This model may be used to evaluate isolator designs for filling oxidation-sensitive products utilizing the correlation between spiking studies and VPHP uptake to minimize the uptake studies required. It could also be used to inform the design of containers that would minimize the potential for VPHP uptake. For the geometry tested here, it was demonstrated that convection only occurs near the top few millimeters of the container. If the fill level is lower, as it would be for a syringe, the diffusion mechanism of transfer predominates and the rate of transfer of HO is much slower. The balance between mass transfer by convection and diffusion should be a consideration in the design of the system to be filled.
开发了一种模型，可用于预测过氧化氢（HO）如何转移到暴露于气相过氧化氢（VPHP）的液体药物产品中。该模型考虑到给定的几何系统和周围条件，通过使用工程学的第一原理，在气相和液相中都考虑了流体流动，以及扩散和对流传质机制，从而预测了从气相转移到液相的 HO 量。该模型用于研究在给定的容器中需要多少空间来消除对流传质，并为在隔离器中填充的卡式瓶或小瓶中的氧化敏感产品创建传质与气/液界面之间的平衡。实验结果与模型预测吻合较好。模型使用了气液两相之间的无滑移边界条件，这对于全注射器尤其重要，因为在全注射器中，对流传质占主导地位。该模型可用于评估利用 spike 研究和 VPHP 吸收之间的相关性来最小化吸收研究所需的填充氧化敏感产品的隔离器设计。它还可以用于告知将最小化 VPHP 吸收潜力的容器设计。对于此处测试的几何形状，证明对流仅发生在容器的前几毫米处。如果填充水平较低，就像注射器那样，转移的扩散机制占主导地位，HO 的转移速率要慢得多。对流和扩散传质之间的平衡应该是填充系统设计的一个考虑因素。
