Application of Feedforward Control Strategy to Optimize the Critical Quality Atributes of Solid Dispersion Formulations: A Case Study of Ginkgo Biloba Leaf Dripping Pills
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引用次数: 0
Abstract
Objectives
As a solid dispersion formulation, dripping pills exhibit significant advantages in enhancing the solubility and bioavailability of poorly soluble drugs. The quality of dripping pills is intrinsically associated with both the formulation solution and operation parameters. However, the conventional post-production quality assessment methods demonstrate limited effectiveness in achieving robust quality control due to their inherent lack of timely feedback mechanisms. It is essential to develop an appropriate method to improve the product quality.
Methods
Based on the concept of quality by design (QbD), this research proposed a feed-forward control strategy to explore the association of critical material attributes (CMAs), critical process parameters (CPPs) and critical quality attributes (CQAs) for Ginkgo biloba leaf dripping pills. The viscosity of dispersing liquid was chosen as CMA, and the drop distance and the drop speed were selected as CPPs. Qualified rate, productivity, and an average weight of dripping pills were proposed as CQAs. Several regression models linking CMA and CPPs to CQAs were established, and the design space of CPPs was defined based on these models.
Results
The coefficients of determination (R2) of all the models were above 0.79. Normal operating ranges were recommended for dispersing liquid viscosity (1.3 ~ 3.1 Pa·s), drop distance (4.5 ~ 6.5 cm), and drop speed (21 ~ 23 d/min). Additionally, the optimized ranges of CPPs can be successfully determined based on the input CMA.
Conclusions
This case study testified that the feedforward control strategy can be applied successfully to compensate for the quality variation of input CMAs, and it is possible to adjust CPPs to accommodate different CMAs for an acceptable range of CQAs, thus achieving quality control of dripping pills and ultimately contributing to the enhancement of product quality consistency.
期刊介绍：
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.
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