3M Drug Delivery Systems, 3M Center, Building 260-3A-05, St. Paul, MN 55144, USA.
Int J Pharm. 2012 Jan 17;422(1-2):101-15. doi: 10.1016/j.ijpharm.2011.10.035. Epub 2011 Oct 21.
A new model has been developed for predicting size distributions delivered from pressurized metered dose inhalers (pMDIs) that contain suspended drug particles. This model enables the residual particle size distribution to be predicted for a broad range of formulations. It expands on previous models by allowing for polydisperse micronized input drug, multiple suspended drugs, dissolved drug, and dissolved or suspended excipient to be included in the formulation. The model indicates that for most pMDI configurations, the majority of droplets contain no drug or a single drug particle and the residual particle size distribution delivered from the pMDI is essentially equivalent to the size distribution of the micronized drug used in the formulation. However, for pMDIs with a high drug concentration or that use small micronized drug particles, there can be a substantial fraction of the droplets that contain multiple drug particles. The residual particle size distribution obtained from these pMDIs can be substantially larger than the size distribution of the micronized drug. Excellent agreement was observed between size distributions predicted using this model and those obtained from experimental cascade impactor measurements (r(2)=0.97), thus demonstrating the ability of the model to accurately predict the size distributions obtained from suspension pMDIs.
已经开发出一种新的模型，用于预测含有悬浮药物颗粒的加压计量吸入器 (pMDI) 输送的粒径分布。该模型能够预测广泛的制剂的剩余粒径分布。它通过允许包含多分散的微粉化输入药物、多种悬浮药物、溶解药物以及溶解或悬浮赋形剂来扩展以前的模型。该模型表明，对于大多数 pMDI 配置，大多数液滴不含药物或仅含有单个药物颗粒，并且从 pMDI 输送的剩余颗粒粒径分布实质上等同于制剂中使用的微粉化药物的粒径分布。然而，对于药物浓度高或使用小粒径微粉化药物颗粒的 pMDI，可能有很大一部分液滴含有多个药物颗粒。从这些 pMDI 获得的剩余颗粒粒径分布可能明显大于微粉化药物的粒径分布。使用该模型预测的粒径分布与从实验级联冲击器测量获得的粒径分布之间观察到极好的一致性（r(2)=0.97），从而证明了该模型能够准确预测悬浮 pMDI 获得的粒径分布的能力。
