| 1. |
- Gabrielsson, Jon, et al.
(author)
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Multivariate methods in the development of a new tablet formulation : optimization and validation
- 2004
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In: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 30:10, s. 1037-1049
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Journal article (peer-reviewed)abstract
- In a previous study of the development of a tablet formulation approximately 100 excipients were characterized in screening experiments using multivariate design. Acceptable values for important responses were obtained with some of the formulations. The relationships between the properties of the excipients and the responses were evaluated using PLS. In this study additional experiments were performed in order to validate models obtained from the screening study and to find a formulation of suitable composition with desired tablet properties. A formulation with the desired disintegration time was found with the additional experiments and the agreement between observed and predicted values was fair for the tablets that did disintegrate. A limitation of this study was that tablets from four experiments did not disintegrate within the set time limit. The lack of agreement between observed and predicted values of these four experiments was probably due to the nature of one of the factors in the design. Considering the reduced experimental design the results are still encouraging.
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| 2. |
- Gabrielsson, Jon, et al.
(author)
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Multivariate Methods in the Development of a New Tablet Formulation : Excipient Mixtures and Principal Properties
- 2006
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In: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 32:1, s. 7-20
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Journal article (peer-reviewed)abstract
- A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material.The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents).As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.
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| 3. |
- Gabrielsson, Jon, et al.
(author)
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Multivariate Methods in the Development of a New Tablet Formulation
- 2003
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In: Drug Development and Industrial Pharmacy. - New York : Marcel Dekker. - 0363-9045 .- 1520-5762. ; 29:10, s. 1053-1075
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Journal article (peer-reviewed)abstract
- The overall objective of this article is to use an efficient approach to find a suitable tablet formulation for direct compression. By using traditional approaches to statistical experimental design in tablet formulation, the number of experiments quickly grows when many descriptive variables or many excipients are included. To facilitate the screening process, a multivariate design, which allows a systematical evaluation of a large number of excipients with a limited number of experiments, was implemented. Formulations with acceptable values for disintegration time and crushing strength were obtained with some of the formulations in the present study. The multivariate experimental design strategy yielded PLS models that will be used to identify a region of interest for the optimization. The strategy is general and can be applied in many different areas of pharmaceutical research and development.
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| 6. |
- Lindberg, Nils-Olof, et al.
(author)
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Use of software to facilitate pharmaceutical formulation : experiences from a tablet formulation
- 2004
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In: Journal of Chemometrics. - Chichester : John Wiley & Sons, Ltd. - 0886-9383 .- 1099-128X. ; 18:3-4, s. 133-138
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Journal article (peer-reviewed)abstract
- This paper exemplifies the benefits of using experimental design together with software to facilitate the formulation of a tablet for specific purposes, from screening to robustness testing. By applying a multivariate design for the screening experiments, many excipients were evaluated in comparatively few experiments. The formulation work was generally based on designed experiments. Most of the experiments were fractional or full factorial designs, generated and evaluated in Modde with the centre point replicated. The robustness of the formulation was evaluated with experimental designs on two different occasions. Tested flavours were found to have limited influence on the important responses, which was key information in order to proceed with that particular composition. The formulation was also robust towards normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. A process step was investigated and, by applying experimental design and keeping in mind previous findings, important information could be gained from the study. The different studies yielded good and very useful models. Established relationships between design factors and responses provided information that was vital for the project. In cases of poor models, essential information regarding robustness was obtained.
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