Mechanistic basis for the effects of process parameters on quality attributes in high shear wet granulation

Three model compounds were used to study the effect of process parameters on in-process critical material attributes and a final product critical quality attribute. The effect of four process parameters was evaluated using design of experiment approach. Batches were characterized for particle size d...

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Bibliographic Details
Published in:International journal of pharmaceutics 2012-12, Vol.439 (1-2), p.324-333
Main Authors: Badawy, Sherif I.F., Narang, Ajit S., LaMarche, Keirnan, Subramanian, Ganeshkumar, Varia, Sailesh A.
Format: Article
Language:English
Subjects:
Alanine - analogs & derivatives
Alanine - chemistry
Compaction
Dissolution
Drug Compounding
experimental design
Granulation parameters
Isoxazoles - chemistry
mechanical properties
Particle Size
particle size distribution
Porosity
Powders - chemistry
Pyrazoles - chemistry
Quality Control
Solubility
Tablets - chemistry
Technology, Pharmaceutical
Triazines - chemistry
Water - chemistry
Wet granulation
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Summary:Three model compounds were used to study the effect of process parameters on in-process critical material attributes and a final product critical quality attribute. The effect of four process parameters was evaluated using design of experiment approach. Batches were characterized for particle size distribution, density (porosity), flow, compaction, and dissolution rate. The mechanisms of the effect of process parameters on primary granule properties (size and density) were proposed. Water amount showed significant effect on granule size and density. The effect of impeller speed was dependent on the granule mechanical properties and efficiency of liquid distribution in the granulator. Blend density was found to increase rapidly during wet massing. Liquid addition rate was the least consequential factor and showed minimal impact on granule density and growth. Correlations of primary properties with granulation bulk powder properties (compaction and flow) and tablet dissolution were also identified. The effects of the process parameters on the bulk powder properties and tablet dissolution were consistent with their proposed link to primary granule properties. Understanding the impact of primary granule properties on bulk powder properties and final product critical quality attributes provides the basis for modulating granulation parameters in order to optimize product performance.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2012.09.011