Department of Pharmaceutics and Food Technology, Complutense University of Madrid, Ramón y Cajal Square, 28040 Madrid, Spain.
Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, 28006 Madrid, Spain.
Int J Pharm. 2019 Jun 30;565:209-218. doi: 10.1016/j.ijpharm.2019.05.011. Epub 2019 May 7.
Roller compaction is a low cost granulation process which application is sometimes limited by the granular loss of compactability and reduced drug dissolution rate. Hence, the design of a robust manufacturing process is key in order to ensure quality of tablets. In this study, for ibuprofen tablets with high drug loading (<7% excipients), the correlations between two critical process parameters (CPPs), namely roller force during granulation and compaction pressure during tabletting, and several critical quality attributes (CQAs) were investigated using a design of experiment (DoE) approach. Multivariate analysis (MVA) was utilized to identify the best regression model to predict CQAs such as disintegration, dissolution, weight uniformity, hardness, porosity and tensile strength for 200 and 600 mg ibuprofen tablets. The tabletting compaction pressure had a greater impact on the aforementioned CQAs than compactor roller force. The Principal Component Analysis (PCA) correlation loading plot showed that compaction pressure was directly related to disintegration time, tensile strength and hardness, and inversely related to both the percentage of drug dissolved and porosity. The inverse correlations were observed for the roller force applied during dry granulation. Amongst all the regression models constructed, multiple linear regression (MLR) showed the best correlation between CPPs and CQAs.
辊压是一种低成本的制粒工艺，但其应用有时会受到颗粒可压缩性损失和药物溶出率降低的限制。因此，设计稳健的制造工艺是确保片剂质量的关键。在这项研究中，对于高载药量（<7%辅料）的布洛芬片剂，使用实验设计（DoE）方法研究了两个关键工艺参数（CPP），即制粒过程中的辊力和压片过程中的压缩压力，以及几个关键质量属性（CQAs）之间的相关性。多元分析（MVA）用于确定最佳回归模型，以预测 200 和 600mg 布洛芬片剂的崩解、溶出、重量均匀性、硬度、孔隙率和拉伸强度等 CQAs。压片压缩压力对上述 CQAs 的影响大于压辊力。主成分分析（PCA）相关加载图显示，压缩压力与崩解时间、拉伸强度和硬度直接相关，与药物溶解百分比和孔隙率成反比。在干法制粒过程中施加的辊力呈反比关系。在所构建的所有回归模型中，多元线性回归（MLR）显示 CPPs 和 CQAs 之间具有最佳相关性。
