Solving a sticking related tablet problem by multivariate statistics and computational tomographic analysis

This work identifies the cause of sticking of granules in an industrial process of tableting. Retrospective multivariate statistical analysis of industrial scale batches' records (PLS, properties and manufacturing conditions of granules and tablets) identified the air flow rate in both granulat...

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Bibliographic Details
Published in:Powder technology 2020-05, Vol.367, p.456-463
Main Authors: Costa, Nuno F., Paulo, Mário G., Diogo, Hermínio P., Pinto, João F.
Format: Article
Language:English
Subjects:
Air flow
Compression
Computer applications
Drying
Flow rates
Flow velocity
Granular materials
Granulation
Laboratories
Moisture content
Multivariate analysis
Multivariate statistical analysis
Process optimization
Process retrospective analysis
Punches
Statistical analysis
Tablets
Tomography
Water content
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Summary:This work identifies the cause of sticking of granules in an industrial process of tableting. Retrospective multivariate statistical analysis of industrial scale batches' records (PLS, properties and manufacturing conditions of granules and tablets) identified the air flow rate in both granulation and drying operations as the critical parameter impacting on sticking. Scaling down the manufacture of tablets to the laboratory scale has allowed the evaluation of the granules' behaviour, that have deformed and fragmented (main mechanism), while converting into tablets. Fragments of granules with high water content in their cores (>2.20%, confirmed by tomography) promoted the sticking of tablets to both dies and punches. In conclusion, the combination of a retrospective analysis of batch records, combined with complementary analysis in the laboratory enabled the identification of the cause of sticking with an increase on manufacture yield from ca 78% in many batches up to >98% for all batches. [Display omitted] •Re-evaluation of medicines that have been granted a valid marketing authorization.•Complementary mechanistic analysis to population analysis of data.•Computational model of the yield of production based on critical process attributes.•Structures of granules clarified by computational tomographic analysis.
ISSN:0032-5910
1873-328X
DOI:10.1016/j.powtec.2020.03.063