An Attempt to Calculate In Silico Disintegration Time of Tablets Containing Mefenamic Acid, a Low Water-Soluble Drug

Based on a Quality by Design (QbD) approach, it is important to follow International Conference on Harmonization (ICH) guidance Q8 (R2) recommendations to explore the design space. The application of an experimental design is, however, not sufficient because of the fact that it is necessary to take...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2013-07, Vol.102 (7), p.2166-2178
Main Authors: Kimura, Go, Puchkov, Maxim, Leuenberger, Hans
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Chemistry, Pharmaceutical
compaction
Computer Simulation
disintegration time
formulation
in silico modeling
Mefenamic Acid - chemistry
Models, Chemical
percolation theory
powder technology
Quality by Design (QbD)
solid dosage form
Solubility
Tablets
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Summary:Based on a Quality by Design (QbD) approach, it is important to follow International Conference on Harmonization (ICH) guidance Q8 (R2) recommendations to explore the design space. The application of an experimental design is, however, not sufficient because of the fact that it is necessary to take into account the effects of percolation theory. For this purpose, an adequate software needs to be applied, capable of detecting percolation thresholds as a function of the distribution of the functional powder particles. Formulation-computer aided design (F-CAD), originally designed to calculate in silico the drug dissolution profiles of a tablet formulation is, for example, a suitable software for this purpose. The study shows that F-CAD can calculate a good estimate of the disintegration time of a tablet formulation consisting of mefenamic acid. More important, F-CAD is capable of replacing expensive laboratory work by performing in silico experiments for the exploration of the formulation design space according to ICH guidance Q8 (R2). As a consequence, a similar workflow existing as best practice in the automotive and aircraft industry can be adopted by the pharmaceutical industry: The drug delivery vehicle can be first fully designed and tested in silico, which will improve the quality of the marketed formulation and save time and money. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2166–2178, 2013
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23541