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Robustness testing of a tablet formulation using multivariate design
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2006 (English)In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 32, no 3, 297-307 p.Article in journal (Refereed) Published
Abstract [en]

A total of 45 experiments were carried out to evaluate the robustness of two similar tablet formulations--a product of two strengths--with respect to normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. The formulations consist of 10 ingredients. Because of the differing amounts of active pharmaceutical ingredients, the two formulations also differ in the amounts of two of the diluents and one of the binders. The excipients and active pharmaceutical ingredient were characterized in terms of multiple variables, and principal properties were calculated with principal component analysis. A Plackett and Burman design was applied to the principal properties. The relationships between the design factors and two responses, mean disintegration time and mean crushing strength, were evaluated by using regression methods. Both formulations were found to be robust under controlled conditions.

Place, publisher, year, edition, pages
Taylor & Francis Group, LLC , 2006. Vol. 32, no 3, 297-307 p.
Keyword [en]
Robustness testing, Plackett-Burman design, multivariate design, PCA, PLS
URN: urn:nbn:se:umu:diva-19041DOI: 10.1080/03639040500518823PubMedID: 16556534OAI: diva2:201219
Available from: 2009-03-03 Created: 2009-03-03 Last updated: 2011-03-11Bibliographically approved
In thesis
1. Multivariate methods in tablet formulation
Open this publication in new window or tab >>Multivariate methods in tablet formulation
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the application of multivariate methods in a novel approach to the formulation of tablets for direct compression. It begins with a brief historical review, followed by a basic introduction to key aspects of tablet formulation and multivariate data analysis. The bulk of the thesis is concerned with the novel approach, in which excipients were characterised in terms of multiple physical or (in most cases) spectral variables. By applying Principal Component Analysis (PCA) the descriptive variables are summarized into a few latent variables, usually termed scores or principal properties (PP’s). In this way the number of descriptive variables is dramatically reduced and the excipients are described by orthogonal continuous variables. This means that the PP’s can be used as ordinary variables in a statistical experimental design. The combination of latent variables and experimental design is termed multivariate design or experimental design in PP’s. Using multivariate design many excipients can be included in screening experiments with relatively few experiments.

The outcome of experiments designed to evaluate the effects of differences in excipient composition of formulations for direct compression is, of course, tablets with various properties. Once these properties, e.g. disintegration time and tensile strength, have been determined with standardised tests, quantitative relationships between descriptive variables and tablet properties can be established using Partial Least Squares Projections to Latent Structures (PLS) analysis. The obtained models can then be used for different purposes, depending on the objective of the research, such as evaluating the influence of the constituents of the formulation or optimisation of a certain tablet property.

Several examples of applications of the described methods are presented. Except in the first study, in which the feasibility of this approach was first tested, the disintegration time of the tablets has been studied more carefully than other responses. Additional experiments have been performed in order to obtain a specific disintegration time. Studies of mixtures of excipients with the same primary function have also been performed to obtain certain PP’s. Such mixture experiments also provide a straightforward approach to additional experiments where an interesting area of the PP space can be studied in more detail. The robustness of a formulation with respect to normal batch-to-batch variability has also been studied.

The presented approach to tablet formulation offers several interesting alternatives, for both planning and evaluating experiments.

Place, publisher, year, edition, pages
Umeå: Kemi, 2004. 56 p.
Organic chemistry, PCA, statistical experimental design, multivariate design, PLS, excipients, direct compression, tablet formulation, robustness testing, Organisk kemi
National Category
Organic Chemistry
Research subject
Organic Chemistry
urn:nbn:se:umu:diva-268 (URN)91-7305-653-7 (ISBN)
Public defence
2004-05-28, KB3B1, KBC, Linneaus väg, Umeå, 09:00
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2011-03-10Bibliographically approved

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Gabrielsson, JonSjöström, Michael
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