Sun Pharmaceutical Industries Ltd.- NDDS, R&D Gurugram, Mumbai, India.
School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, India.
Curr Pharm Des. 2018;24(13):1434-1445. doi: 10.2174/1381612824666180403115106.
The objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherwise may not be possible through single type of technology.
Risk assessment studies were carried out to identify probable risks influencing CQAs on the product. In design of experiments (DoE), the process parameters (independent variables) i.e., chiller temperature X1, High Pressure Homogenization (HPH) pressure X2, and HPH cycles X3 were optimized using a three-factor two level face-centered central composite design to streamline the influence on three responses, namely encapsulation efficiency Y1, particle size Y2 and outlet temperature Y3. Independent and dependent variables were analyzed to establish a full-model second-order polynomial equation. F value is used to confirm the omission of insignificant parameters/interactions to derive a reduced-model polynomial equation to predict the Y1, Y2 and Y3 for optimized moxifloxacin in situ gelled nanosuspension.
Desirability plots showed the effects of X1, X2, and X3 on Y1, Y2 and Y3, respectively. The design space is generated to obtain optimized process parameters viz. chiller temperature (-5°C), HPH pressure 800 - 900 bar and 8 cycles that resulted in nanosuspension with ≈ 500 nm size, encapsulation efficiency >65% and final formulation temperature <23°C that were necessary to maintain the formulation in a liquid state.
Quality by Design (QbD) approach is recently been encouraged by regulatory bodies to improve the quality of the finished product. This approach proved to be a useful tool in the development of robust nanosuspension of highly hydrophilic drugs with improved efficiency. Results indicate that such hybrid gel systems can be used to control the release of SLNs from application site and prolong their action in a sustained manner.
本研究旨在应用质量源于设计（QbD）原理，对亲水药物盐酸莫西沙星（MOX）的混合递药系统（固体脂质纳米粒（SLNs）和原位凝胶系统的组合）的工艺参数进行优化，以实现其控制释放，否则单靠一种技术可能无法实现。
进行风险评估研究，以确定可能影响产品关键质量属性（CQAs）的潜在风险。在实验设计（DoE）中，使用三因素两水平的中心复合面设计优化工艺参数（自变量），即冷却器温度 X1、高压匀质压力 X2 和高压匀质循环 X3，以简化对三个响应的影响，即包封效率 Y1、粒径 Y2 和出口温度 Y3。分析独立变量和依赖变量，建立完整模型二阶多项式方程。F 值用于确认是否有不重要的参数/相互作用被忽略，以得出简化模型多项式方程，预测优化的莫西沙星原位凝胶纳米混悬液的 Y1、Y2 和 Y3。
期望图显示了 X1、X2 和 X3 对 Y1、Y2 和 Y3 的影响。生成设计空间以获得优化的工艺参数，即冷却器温度（-5°C）、高压匀质压力 800-900 巴和 8 个循环，这使得纳米混悬剂的粒径约为 500nm，包封效率>65%，最终制剂温度<23°C，这是保持制剂处于液态所必需的。
质量源于设计（QbD）方法最近受到监管机构的鼓励，以提高成品质量。该方法被证明是一种有用的工具，可用于开发高效的高亲水性药物的稳健纳米混悬剂。结果表明，这种混合凝胶系统可用于控制 SLNs 从应用部位的释放，并以持续的方式延长其作用。
