a Department of Pharmaceutical Technology, Faculty of Pharmacy , Gazi University , Etiler , Ankara , Turkey.
Drug Dev Ind Pharm. 2018 Dec;44(12):1905-1917. doi: 10.1080/03639045.2018.1496450. Epub 2018 Sep 10.
The main objective of this study was the development of pH-independent controlled release valsartan matrix tablet in Quality by design (QbD) framework. The quality target product profile (QTPP), critical quality attributes (CQAs) and critical material attributes (CMAs) were defined by science and risk-based methodologies. Potential risk factors were identified with Fishbone diagram. Following, CMAs were further investigated with a semi-quantitative risk assessment method, which has been revised with mitigated risks after development and optimization studies. According to defined critical material attributes, which one of them was determined to be the dissolution, formulation optimization study was performed by using a statistical design of experiment. Formulation variables have been identified and fixed first with a 'One factor at a time (OFAT)' approach. After OFAT studies, a statistical experimental design was conducted with the most critical material attributes. Statistical design space and mathematical prediction equations have been developed for dissolution and hardness, which is important to predict drug dissolution behavior. In conclusion, a pH-independent release has been achieved for weakly acidic drug valsartan with a deeper understanding of drug product quality, with the science and risk-based approaches of QbD tools.
本研究的主要目的是在质量源于设计（QbD）框架下开发 pH 非依赖性缬沙坦控释骨架片。通过科学和基于风险的方法来定义质量目标产品概况（QTPP）、关键质量属性（CQAs）和关键物料属性（CMAs）。采用鱼骨图识别潜在风险因素。随后，采用半定量风险评估方法进一步研究 CMAs，并在开发和优化研究后降低风险。根据定义的关键物料属性，其中一个被确定为溶出度，通过使用统计实验设计进行制剂优化研究。首先采用单因素法（OFAT）确定制剂变量并固定。在 OFAT 研究之后，采用最关键的物料属性进行统计实验设计。开发了溶出度和硬度的统计设计空间和数学预测方程，这对于预测药物溶出行为很重要。总之，通过基于科学和风险的 QbD 工具，对弱酸性药物缬沙坦实现了 pH 非依赖性释放，深入了解了药物产品质量。
