Cespi Marco, Perinelli Diego R, Casettari Luca, Bonacucina Giulia, Caporicci Giuseppe, Rendina Filippo, Palmieri Giovanni F
School of Pharmacy, University of Camerino, via S. Agostino 1, 62032 Camerino, MC, Italy.
Department of Biomolecular Sciences, University of Urbino, Piazza Rinascimento 6, PU, 61029 Urbino, Italy.
Int J Pharm. 2014 Dec 30;477(1-2):140-7. doi: 10.1016/j.ijpharm.2014.10.009. Epub 2014 Oct 7.
The use of process analytical technologies (PAT) to ensure final product quality is by now a well established practice in pharmaceutical industry. To date, most of the efforts in this field have focused on development of analytical methods using spectroscopic techniques (i.e., NIR, Raman, etc.). This work evaluated the possibility of using the parameters derived from the processing of in-line raw compaction data (the forces and displacement of the punches) as a PAT tool for controlling the tableting process. To reach this goal, two commercially available formulations were used, changing the quantitative composition and compressing them on a fully instrumented rotary pressing machine. The Heckel yield pressure and the compaction energies, together with the tablets hardness and compaction pressure, were selected and evaluated as discriminating parameters in all the prepared formulations. The apparent yield pressure, as shown in the obtained results, has the necessary sensitivity to be effectively included in a PAT strategy to monitor the tableting process. Additional investigations were performed to understand the criticalities and the mechanisms beyond this performing parameter and the associated implications. Specifically, it was discovered that the efficiency of the apparent yield pressure depends on the nominal drug title, the drug densification mechanism and the error in pycnometric density. In this study, the potential of using some parameters derived from the compaction raw data has been demonstrated to be an attractive alternative and complementary method to the well established spectroscopic techniques to monitor and control the tableting process. The compaction data monitoring method is also easy to set up and very cost effective.
如今，使用过程分析技术（PAT）来确保最终产品质量在制药行业已是一种成熟的做法。迄今为止，该领域的大部分工作都集中在开发使用光谱技术（即近红外、拉曼等）的分析方法上。这项工作评估了将在线原料压片数据处理得到的参数（冲头的力和位移）用作控制压片过程的PAT工具的可能性。为实现这一目标，使用了两种市售制剂，改变其定量组成并在一台完全配备仪器的旋转压片机上进行压片。选择并评估了赫克尔屈服压力、压实能量以及片剂硬度和压实压力，将其作为所有制备制剂中的鉴别参数。如所得结果所示，表观屈服压力具有必要的灵敏度，可有效纳入PAT策略以监测压片过程。还进行了额外的研究，以了解这一性能参数背后的关键因素和机制以及相关影响。具体而言，发现表观屈服压力的效率取决于标称药物含量、药物致密化机制和比重瓶密度误差。在本研究中，已证明使用一些来自压片原始数据的参数作为一种有吸引力的替代方法和补充方法，可用于监测和控制压片过程，以补充成熟的光谱技术。压片数据监测方法也易于设置且成本效益很高。
