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从富含 API 的材料性质库中预测性地开发用于重量给料的粉末。

Development of a predictive model for gravimetric powder feeding from an API-rich materials properties library.

机构信息

Worldwide Research and Development, Pfizer Inc, Sandwich, Kent, UK.

Worldwide Research and Development, Pfizer Ltd, Mumbai, India.

出版信息

Int J Pharm. 2022 Sep 25;625:122071. doi: 10.1016/j.ijpharm.2022.122071. Epub 2022 Aug 3.

DOI:10.1016/j.ijpharm.2022.122071
PMID:35931397
Abstract

A model was developed for predicting the feed factor profile of a powder, processed through a gravimetric feeder, as a function of material properties and process parameters. Predictive models proposed in existing literature have often used excipients and active pharmaceutical ingredients (APIs) with good powder flow characteristics in their development. In this work, a material properties library containing a large proportion of APIs, as well as excipients and co-processed blends, was used to build the model and enhance the prediction of feed factor profile for cohesive powders. Gravimetric feeder trials were performed at varying mass flow rates and screw geometries to determine the feed factor profiles. A semi-empirical exponential model, with parameters f, f, and β, was then used to fit the experimental feed factor profiles. Bayesian optimisation and Support Vector Regression (SVR) modelling techniques were utilised to optimise and predict the exponential model parameters as a function of material properties. The parameters found to strongly influence the model were particle size, bulk density, FFC and FT4 rheometer parameters. Results showed low prediction errors between the estimated and experimental data. The final model produces good estimations of the feed factor profile and requires minimal powder consumption.

摘要

建立了一个模型,以预测通过重量给料器处理的粉末的给料因子分布,该模型是作为材料特性和工艺参数的函数。现有文献中提出的预测模型在开发过程中通常使用具有良好粉末流动特性的赋形剂和活性药物成分(API)。在这项工作中,使用了一个包含大量 API 以及赋形剂和共加工混合物的材料特性库来建立模型,以增强对粘性粉末给料因子分布的预测。在不同的质量流速和螺杆几何形状下进行重量给料器试验,以确定给料因子分布。然后,使用半经验指数模型,带有参数 f、f 和 β,来拟合实验给料因子分布。利用贝叶斯优化和支持向量回归(SVR)建模技术,优化和预测指数模型参数作为材料特性的函数。发现对模型有强烈影响的参数是粒径、堆密度、FFC 和 FT4 流变仪参数。结果表明,估计数据和实验数据之间的预测误差较小。最终模型能够很好地估计给料因子分布,且需要的粉末消耗很少。

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