Thomas V Hayden, Naath Maryanne
Research Formulations, Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, USA.
Int J Pharm. 2008 Jul 9;359(1-2):150-7. doi: 10.1016/j.ijpharm.2008.03.043. Epub 2008 Apr 8.
To accelerate clinical formulation development, an excipient compatibility screen should be conducted as early as possible and it must be rapid, robust and resource sparing. This however, does not describe the traditional excipient compatibility testing approach, requiring many tedious and labor intensive manual operations. This study focused on transforming traditional practices into a completely automated screening process to increase sample throughput and realign resources to more urgent areas, while maintaining quality. Using the developed system, a complete on-line performance study was conducted whereby drug-excipient mixtures were weighed, blended and subjected to accelerated stress stability for up to 1 month, followed by sample extraction and HPLC analysis. Compared to off-line traditional study protocols, the system provided similar relative rank order results with equivalent precision and accuracy, while increasing sample throughput. The designed system offers a resource sparing primary screen for drug-excipient chemical compatibility for solid dosage form development. This approach allows risk assessment analysis, based upon formulation complexity, to be conducted prior to the commitment of resources and candidate selection for clinical development.
为加速临床制剂开发，应尽早进行辅料相容性筛选，且该筛选必须快速、可靠且节省资源。然而，这并非传统的辅料相容性测试方法，传统方法需要许多繁琐且 labor intensive（此处可能有误，推测为labor-intensive，意为劳动密集型）的手动操作。本研究专注于将传统做法转变为完全自动化的筛选过程，以提高样品通量，并将资源重新分配到更紧急领域，同时保证质量。使用所开发的系统，进行了一项完整的在线性能研究，在此过程中对药物-辅料混合物进行称重、混合，并进行长达1个月的加速应力稳定性试验，随后进行样品提取和高效液相色谱分析。与离线传统研究方案相比，该系统提供了具有同等精密度和准确度的类似相对排序结果，同时提高了样品通量。所设计的系统为固体剂型开发中的药物-辅料化学相容性提供了一种节省资源的初步筛选方法。这种方法允许在投入资源和选择临床开发候选物之前，基于制剂复杂性进行风险评估分析。
