Document Detail

De-risking pharmaceutical tablet manufacture through process understanding, latent variable modeling, and optimization technologies.
MedLine Citation:
PMID:  21969245     Owner:  NLM     Status:  MEDLINE    
In pharmaceutical tablet manufacturing processes, a major source of disturbance affecting drug product quality is the (lot-to-lot) variability of the incoming raw materials. A novel modeling and process optimization strategy that compensates for raw material variability is presented. The approach involves building partial least squares models that combine raw material attributes and tablet process parameters and relate these to final tablet attributes. The resulting models are used in an optimization framework to then find optimal process parameters which can satisfy all the desired requirements for the final tablet attributes, subject to the incoming raw material lots. In order to de-risk the potential (lot-to-lot) variability of raw materials on the drug product quality, the effect of raw material lot variability on the final tablet attributes was investigated using a raw material database containing a large number of lots. In this way, the raw material variability, optimal process parameter space and tablet attributes are correlated with each other and offer the opportunity of simulating a variety of changes in silico without actually performing experiments. The connectivity obtained between the three sources of variability (materials, parameters, attributes) can be considered a design space consistent with Quality by Design principles, which is defined by the ICH-Q8 guidance (USDA 2006). The effectiveness of the methodologies is illustrated through a common industrial tablet manufacturing case study.
Koji Muteki; Vidya Swaminathan; Sonja S Sekulic; George L Reid
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Publication Detail:
Type:  Journal Article     Date:  2011-10-04
Journal Detail:
Title:  AAPS PharmSciTech     Volume:  12     ISSN:  1530-9932     ISO Abbreviation:  AAPS PharmSciTech     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-29     Completed Date:  2012-03-26     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100960111     Medline TA:  AAPS PharmSciTech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1324-34     Citation Subset:  IM    
Pfizer Global Research & Development, Groton, Connecticut 06340, USA.
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MeSH Terms
Chemistry, Pharmaceutical
Computer Simulation*
Drug Compounding
Least-Squares Analysis*
Models, Chemical*
Pharmaceutical Preparations / chemistry*,  standards
Quality Control
Technology, Pharmaceutical / methods*,  standards
Reg. No./Substance:
0/Pharmaceutical Preparations; 0/Tablets

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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