Avalle P, Pollitt M J, Bradley K, Cooper B, Pearce G, Djemai A, Fitzpatrick S
MSD Werthenstein Biopharma, Industrie Nord, 1, Schachen (LU), Switzerland.
MSD, Hoddesdon, United Kingdom.
Eur J Pharm Biopharm. 2014 Jul;87(2):244-51. doi: 10.1016/j.ejpb.2014.01.008. Epub 2014 Feb 3.
This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements.
本研究聚焦于在质量源于设计（QbD）框架内对控释（CR）微丸产品制造过程的控制。制造工艺为Wurster包衣：首先将活性药物成分（API）分层涂覆在糖丸芯上，其次进行控释（CR）包衣。对于这两个步骤中的每一步，均讨论了过程分析技术（PAT）方法的开发，以及将自动显微镜作为参考方法的新应用。最终，PAT方法应与产品性能相关联，并且该CR产品的两个关键关键质量属性（CQA）分别是含量测定和释放速率，分别与API和CR包衣步骤相关。在本研究中，通过化学计量学在中试规模工业环境中的包衣过程中探索了近红外（NIR）光谱与这些属性之间的联系。建立了NIR光谱与包衣重量（用于API量）、CR包衣厚度和溶出性能之间的相关性。这些相关性使得能够在线监测包衣过程，从而更好地根据QbD要求控制产品性能。
