Kopsch Thomas, Murnane Darragh, Symons Digby
University of Cambridge, Department of Engineering, Trumpington Street, CB2 1PZ, UK.
University of Hertfordshire, Department of Pharmacy, Pharmacology and Postgraduate Medicine, College Lane, AL10 9AB, UK.
Int J Pharm. 2017 Aug 30;529(1-2):589-596. doi: 10.1016/j.ijpharm.2017.07.002.
In dry powder inhalers (DPIs) the patient's inhalation manoeuvre strongly influences the release of drug. Drug release from a DPI may also be influenced by the size of any air bypass incorporated in the device. If the amount of bypass is high less air flows through the entrainment geometry and the release rate is lower. In this study we propose to reduce the intra- and inter-patient variations of drug release by controlling the amount of air bypass in a DPI. A fast computational method is proposed that can predict how much bypass is needed for a specified drug delivery rate for a particular patient. This method uses a meta-model which was constructed using multiphase computational fluid dynamic (CFD) simulations. The meta-model is applied in an optimization framework to predict the required amount of bypass needed for drug delivery that is similar to a desired target release behaviour. The meta-model was successfully validated by comparing its predictions to results from additional CFD simulations. The optimization framework has been applied to identify the optimal amount of bypass needed for fictitious sample inhalation manoeuvres in order to deliver a target powder release profile for two patients.
在干粉吸入器（DPI）中，患者的吸入动作对药物释放有很大影响。DPI的药物释放也可能受到装置中任何空气旁路大小的影响。如果旁路量很大，那么通过夹带结构的空气流量就会减少，释放速率也会降低。在本研究中，我们提议通过控制DPI中的空气旁路量来减少患者内和患者间药物释放的差异。我们提出了一种快速计算方法，该方法可以预测特定患者达到指定药物递送速率所需的旁路量。此方法使用一个元模型，该元模型是通过多相计算流体动力学（CFD）模拟构建的。该元模型应用于一个优化框架中，以预测实现类似于期望目标释放行为的药物递送所需的旁路量。通过将其预测结果与其他CFD模拟结果进行比较，该元模型得到了成功验证。该优化框架已被应用于确定虚拟样本吸入动作所需的最佳旁路量，以便为两名患者提供目标粉末释放曲线。
