Blue Nile Pharmaceutical Company, Khartoum, Sudan.
Int J Pharm. 2012 Feb 28;423(2):167-78. doi: 10.1016/j.ijpharm.2011.12.024. Epub 2011 Dec 23.
The focus of the current investigations was to apply quality by design (QbD) approach to the development of dispersible tablets. Critical material and process parameters are linked to the critical quality attributes of the product. Variability is reduced by product and process understanding which translates into quality improvement, risk reduction and productivity enhancement. The risk management approach further leads to better understanding of the risks, ways to mitigate them and control strategy is proposed commensurate with the level of the risk. Design space in combination with pharmaceutical quality management system provide for flexible regulatory approaches with opportunity for continuous improvement that benefit patient and manufacturer alike. The development of dispersible tablet was proposed in the current study through a QbD paradigm for a better patient compliance and product quality. The quality target product profile of a model biopharmaceutical class II drug was identified. Initial risk analysis led to the identification of the critical quality attributes. Physicochemical characterization and compatibility studies of the drug with commonly used excipients were performed. Experiments were designed with focus on critical material and process attributes. Design space was identified and risk factors for all the possible failure modes were below critical levels after the implementation of control strategy. Compliance to the design space provides an opportunity to release batches in a real time. In conclusion, QbD tools together with risk and quality management tools provided an effective and efficient paradigm to build the quality into dispersible tablet.
本研究旨在将质量源于设计（QbD）理念应用于分散片的开发。关键物料和工艺参数与产品的关键质量属性相关联。通过对产品和工艺的深入了解，可以降低变异性，从而实现质量改进、风险降低和生产效率提高。风险管理方法进一步加深了对风险的理解，提出了减轻风险的方法和相应的控制策略，与风险水平相适应。设计空间与药品质量管理体系相结合，为灵活的监管方法提供了机会，促进了持续改进，使患者和制造商都受益。本研究通过 QbD 范式提出了分散片的开发，以提高患者的顺应性和产品质量。确定了模型生物制药 II 类药物的质量目标产品概况。初步风险分析确定了关键质量属性。对药物与常用赋形剂的理化特性和相容性进行了研究。实验设计侧重于关键的物料和工艺属性。确定了设计空间，并在实施控制策略后，所有可能失效模式的风险因素均低于临界水平。符合设计空间为实时放行批次提供了机会。总之，QbD 工具以及风险管理工具提供了一种有效和高效的方法，将质量融入到分散片的开发中。
