应用前馈控制策略优化固体分散制剂关键质量属性——以银杏叶滴丸为例

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2025-09-30 DOI:10.1007/s12247-025-10114-4

Xiaoping Wang, Jichen Shen, Sijun Wu, Haibin Qu

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引用次数: 0

摘要

目的滴丸作为一种固体分散制剂，在提高难溶性药物的溶解度和生物利用度方面具有显著的优势。滴丸的质量与制剂溶液和操作参数有内在联系。然而，由于缺乏及时的反馈机制，传统的后期质量评估方法在实现稳健的质量控制方面的有效性有限。开发一种合适的方法来提高产品质量是至关重要的。方法基于设计质量（QbD）理念，提出一种前馈控制策略，探讨银杏叶滴丸的关键材料属性（CMAs）、关键工艺参数（CPPs）和关键质量属性（cqa）之间的关联。以分散液粘度为CMA，以滴距和滴速为CPPs。提出了滴丸的合格率、产率和平均质量作为cqa。建立了将CMA和cps与cqa联系起来的回归模型，并在此基础上定义了cps的设计空间。结果各模型的决定系数（R2）均在0.79以上。分散液粘度推荐在1.3 ~ 3.1 Pa·s，滴距推荐在4.5 ~ 6.5 cm，滴速推荐在21 ~ 23 d/min。此外，基于输入CMA可以成功地确定cps的优化范围。结论该前馈控制策略可成功补偿输入cma的质量变化，并可在可接受的cqa范围内调整cps以适应不同的cma，从而实现滴丸的质量控制，最终提高产品的质量一致性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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Application of Feedforward Control Strategy to Optimize the Critical Quality Atributes of Solid Dispersion Formulations: A Case Study of Ginkgo Biloba Leaf Dripping Pills

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.

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

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.