基于QbD的薄膜包衣质量影响因素的分析_—以清咽滴丸为例毕业论文.doc

PAGE \* MERGEFORMAT 43 摘 要 保证药品质量事关千万患者的用药安全，也是药品生产企业赖以生存的根本，更是企业肩负的重要责任。对于药品质量出现的问题，如何运用科学的手段和方法解决质量问题，保证药品质量的稳定性，保障患者用药安全，是本论文研究的目的和意义。 本文作者在查阅文献并理解薄膜包衣工艺技术的基础上，运用质量源于设计（QbD）的理念和方法，在“素丸的组成和性质、包衣溶液的处方、包衣操作条件及产品贮藏的环境”四类薄膜包衣质量建立的基础中，确定了清咽滴丸关键质量属性—性状的影响因素是素丸化料温度、滴制温度、热风柜设定温度、包衣锅滚筒转速、蠕动泵频率、负压及丸床温度，其中关键因素是负压及丸床温度；同时在关键工艺过程—包衣工序中确定和验证了负压和丸床温度的参数控制范围，进而控制了包衣工艺可能出现的偏差，最终达到更新工艺以解决清咽滴丸析晶的质量问题，并保证了产品质量的稳定性。 变更后的清咽滴丸薄膜包衣工艺能有效解决清咽滴丸析晶的质量问题，确保产品质量的稳定性；同时为其它中药生产企业在解决类似质量问题时提供了可以参考的思路和方法。 关键词：清咽滴丸，QbD，薄膜包衣工艺，丸床温度，负压 Analysis of Factors Affecting Film Coating Quality Based on QbD — Taking Qingyan Dropping Pill for Example Drug quality is directly linked to the safety of patients and decides whether pharmaceutical companies can survive and succeed. This paper aims to discuss how to use science based approach to solve the technical issues during drug manufacturing and ensure the quality standards are consistently met for the safety of patients. The author, after reviewing related literature on film coating technology, and adopting the concept of ‘quality by design (QbD)’, concluded 1). there are four aspects of quality of thin film coating, i.e. composition and property of the core, composition of coating solution, coating conditions, and storage environment of product, 2) factors that affect the critical quality attributes of Qingyan dropping pill are dissolution temperature, dripping temperature, inlet air temperature, pan speed, peristaltic pump’s frequency (flow rate), negative pressure, and temperature of pill bed. Among them, the key factors are negative pressure and temperature of pill bed. Through control of negative pressure range and pill bed temperature deviation of coating processes has been minimized to eventually solve the quality issue of Qingyan dropping pill crystallization, so as to ensure quality standards are consistently met. . In conclusion, the experiments and methodology discussed in this thesis not only resolved the crystallization issue during film