The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance
The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance
复制标题
颗粒密度对压片和药品性能的影响
DOI：
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发表时间：
2017
影响因子：
3.7
通讯作者：
Daniel J. Goodwin
中科院分区：
文献类型：
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作者：
S. Ban;Daniel J. Goodwin
摘要目的研究高剪切湿法制粒工艺中颗粒致密化对压片质量和产品性能的影响。产品性能标准需要与提供可生产性标准的需求相平衡，以确保稳健的工业规模片剂生产工艺。A质量设计方法被用来确定压片过程中的控制规格，提出了一个设计空间的崩解和溶解，并了解允许的操作限制和所需的控制为工业压片process.MethodsGranules的密度（填充密度）不同的水加入量，喷雾速率，和湿成团时间的实验设计（DoE）的方法。将颗粒压制成片剂至一定厚度范围，以获得不同断裂力的片剂。评价所制备片剂的崩解和溶出性能。颗粒填充密度对压片的影响是合理的压缩性，压片性和compactibility.ResultsTabletting和产品的性能标准提供了竞争的孔隙率要求。颗粒填充密度的增加影响了可压片性和可重复性，并限制了获得具有足够机械强度的片剂的能力。片剂固体分数增加（孔隙率降低）影响崩解时限和溶出度。一个基于属性的设计空间崩解和溶解指定实现产品性能和manufacturability.ConclusionThe方法制粒和所得颗粒填充密度是一个关键的设计考虑，以实现现代工业规模的药品生产和分销所需的产品性能和可制造性。
ABSTRACTPurposeThe impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process.MethodsGranules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility.ResultsTabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability.ConclusionThe method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.