| 1. |
- Gabrielsson, Jon, et al.
(författare)
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Combining process and spectroscopic data to improve batch modeling
- 2006
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Ingår i: AIChE Journal. - : Wiley. - 0001-1541 .- 1547-5905. ; 52:9, s. 3164-72
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical production is at present characterized by static processes where quality is guaranteed by controlling the purity of the final product. Achieving better control throughout the process, as a means for improving product quality, is one of the objectives of the PAT initiative by the FDA. A data set consisting of 11 batches characterized by UV spectroscopy together with process data was used in this study. Design of experiments was used to introduce controlled process variation in test batches. The objective was to investigate possible advantages of MSPC using a combined data set, compared to separate models of the respective data sets. Individual models for the separate data sets show that they contain complementary information. A major advantage of combining spectroscopic and process data is that deviations that would go unnoticed using just an individual model can be detected and interpreted. All process manipulations were detected by the combined data set model. Implementation of these methods to batch processes in primary and secondary pharmaceutical production is feasible. An enhanced understanding of the process together with control tools should lead to a well-understood process and, ultimately, real time release. © 2006 American Institute of Chemical Engineers AIChE J, 2006
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| 2. |
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| 3. |
- Gabrielsson, Jon, 1973-
(författare)
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Multivariate methods in tablet formulation
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate methods in the development of a new tablet formulation : optimization and validation
- 2004
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 30:10, s. 1037-1049
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation : Excipient Mixtures and Principal Properties
- 2006
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 32:1, s. 7-20
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation
- 2003
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Ingår i: Drug Development and Industrial Pharmacy. - New York : Marcel Dekker. - 0363-9045 .- 1520-5762. ; 29:10, s. 1053-1075
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Tidskriftsartikel (refereegranskat)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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| 7. |
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| 8. |
- Gabrielsson, Jon, et al.
(författare)
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OPLS methodology for analysis of pre-processing effects on spectroscopic data
- 2006
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439. ; 84:1-2, s. 153-8
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Tidskriftsartikel (refereegranskat)abstract
- Pre-processing of spectroscopic data is commonly applied to remove unwanted systematic variation. Possible loss of information and ambiguity regarding discarded variation are issues that complicate pre-treatment of data. In this paper, OPLS methodology is applied to evaluate different techniques for pre-processing of spectroscopic data gathered from a batch process. The objective is to present a rational scheme for analysis of pre-processing in order to understand the influence and effect of pre-treatment.O2PLS uses linear regression to divide the systematic variation in X and Y into three parts; one part with joint X–Y covariation, i.e. related to both X and Y, one part of X with Y-orthogonal variation and one part of Y with X-orthogonal variation.All of the investigated pre-treatment methods removed an additive baseline as expected. In the analysis of raw and differentiated data variation associated with the baseline was found in the Y-orthogonal part of X. Orthogonal information was also found in Y, which suggests that this pre-processing procedure not only removed variation. This would have been more difficult to detect without the O2PLS model since both raw and differentiated data must be analysed simultaneously.Development of a knowledge based strategy with OPLS methodology is an important step towards eliminating trial and error approaches to pre-processing.
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| 9. |
- Gabrielsson, Jon, et al.
(författare)
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Recent Developments in Multivariate Calibration
- 2006
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Ingår i: Critical Reviews in Analytical Chemistry. - : Informa UK Limited. - 1040-8347 .- 1547-6510. ; 36:3-4, s. 243-55
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Tidskriftsartikel (refereegranskat)abstract
- This review covers the area of multivariate calibration; from pre-processing of data prior to modeling and applications of regression methods for calibration and prediction. The importance of pre-treatment of data is highlighted with many of the recently developed methods together with traditional methods. Several articles provide comparisons between different pre-processing methods. Methods for data from coupled chromatographic methods, which have found increasing use and where data pre-processing is a prerequisite for multivariate modeling, are also included. Many of the novel chemometric methods deal with model complexity and interpretation. A diverse set of applications are also presented and references are also given to early papers, making it possible to acquire a deeper knowledge of methods of interest.
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| 10. |
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| 11. |
- Gabrielsson, Jon, et al.
(författare)
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The OPLS methodology for analysis of multi-block batch process data
- 2006
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Ingår i: Journal of Chemometrics. - : Wiley. - 0886-9383 .- 1099-128X. ; 20:8-10, s. 362-9
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Tidskriftsartikel (refereegranskat)abstract
- With increasing availability of different process analysers multiple data sources are commonly available and this will impose new challenges and enable new types of investigations. The ability to separate joint, complementary and redundant information in multiple block data will be of increasing importance. In this study data from a batch mini plant were collected and O2PLS was implemented to facilitate a combined analysis of spectroscopic and process data. This enables assessment of both the joint and complementary variations in the respective data sets. The different types of variation that were separated were then modelled together to evaluate their individual correlation to a time response. By combining data of different origin an uncomplicated summary of the variation was accomplished and a deeper understanding of process interactions was gained. The analysis of separated variation with a response variable proved useful for verifying the supposed correlation between the joint variation and time.
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| 12. |
- Jonsson, Hans, et al.
(författare)
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Evaluation of Preprocessing Methods
- 2009
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Ingår i: Comprehensive Chemometrics. - AMSTERDAM : Elsevier. - 9780444527028 ; , s. A199-A206
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Lindberg, Nils-Olof, et al.
(författare)
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Use of software to facilitate pharmaceutical formulation : experiences from a tablet formulation
- 2004
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Ingår i: Journal of Chemometrics. - Chichester : John Wiley & Sons, Ltd. - 0886-9383 .- 1099-128X. ; 18:3-4, s. 133-138
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Lundstedt, Erik Torbjörn, et al.
(författare)
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Metabolic profiles
- 2012
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Patent (populärvet., debatt m.m.)abstract
- The invention relates to the use of endogenous metabolites to produce a metabolic profile of a disorder or disease in a subject, e.g. an autoimmune disease, in particular rheumatoid arthritis, and the analysis of such metabolic profiles in order to find disturbances in such profiles in a subject which are caused by or correlated with the said diseases or disorders. Such disturbances can be normalised by treatment of the subject with specified compounds, particularly N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidine or an aminoguanidine.
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| 15. |
- Lundstedt-Enkel, Katrin, et al.
(författare)
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Different multivariate approaches to material discovery, process development, PAT and environmental process monitoring
- 2006
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439 .- 1873-3239. ; 84:1-2, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- The aim with the present paper is to illustrate the use of multivariate strategies (i.e. integration of different multivariate methods) with five examples, four from the pharmaceutical industry and one from environmental research. In the first part, two examples wherein hierarchical models are applied to quality control (QC) and process control are discussed. In the second part a more complex problem and a strategy for material discovery/development are presented wherein a combination of multivariate calibration, multivariate analysis and multivariate design is needed. In the third part, a process analytical/optimization problem is illustrated with a two-step process, demanding that different multivariate tools are combined in a sequential way so that a useful model can be established and the process can be understood. In the final part the usefulness of principal component analysis followed by soft independent modelling of class analogy is illustrated with an example from environmental process monitoring. The five examples from quite different areas show that the chemometric tools are even more powerful if used integrated. However, different strategies and combinations of the tools have to be applied, depending on the problem and the aim.
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| 16. |
- Lundstedt, Torbjörn, et al.
(författare)
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Dynamic modelling of time series data in nutritional metabonomics : A powerful complement to randomized clinical trials in functional food studies
- 2010
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier B V. - 0169-7439 .- 1873-3239. ; 104:1, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Functional foods are foods or dietary ingredients that provide a health benefit beyond basic nutrition. A new legislation, known as the Nutrition and Health Claims Regulation, defines the legal framework for such claims within the European Union. Any claim about the nutritional or physiological effects of a product must be scientifically demonstrated. In this study, we have focused on the exploration of metabonomics as a complementary profiling technology to establish monitoring/data analysis procedures of randomized nutritional trials. More specifically, a combined intake of soybean and grapefruit in a human intervention study was analyzed with respect to both pharmacological and physiological effects. Resulting multivariate models showed a diet-induced decrease of lactate, cholesterols and triglycerides. The most drastically elevated metabolite, myo-inositol, was found to accompany a marked reduction of triglyceride levels. Suggestively, this is due to the biotransformation of myo-inositol to phosphatidylinositol, which results in a decrease of available precursors to form triglycerides. Strong inter-subject variation was present that required special attention. Dynamic modelling of collected time series data that provided the opportunity to identify slow, medium or fast responders as well as groups of subjects showing different response profiles, was also highlighted in the study. The applied strategy of time series data has proven to be a powerful complement to randomized nutritional studies adopting a clinical trial design.
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| 17. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 18. |
- Rodgers, Waymond, et al.
(författare)
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Combining experiential and conceptual learning in accounting education : A review with implications
- 2017
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Ingår i: Management Learning. - London : Sage Publications. - 1350-5076 .- 1461-7307. ; 48:2, s. 187-205
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Tidskriftsartikel (refereegranskat)abstract
- Within accounting education, both conceptual and experiential learning have been important learning approaches. However, while experiential learning has been extensively studied in accounting education, the critical role of conceptual learning has received considerably less attention. In this article, we review theory and research to develop a framework involving the Throughput Model that relates to both conceptual and experiential learning. Based on our review and combination, we suggest implications for the design and implementation of accounting education. © The Author(s) 2016.
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| 19. |
- Trygg, Johan, et al.
(författare)
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Background estimation, denoising, and preprocessing
- 2009. - 2
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Ingår i: Comprehensive chemometrics. - Amsterdam : Elsevier. - 9780444641663 - 9780444527028 - 9780444641656 ; , s. 137-141
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Bokkapitel (refereegranskat)abstract
- This chapter gives a background and an introduction to methods commonly used for data preprocessing; from traditional methods to recently developed model-based approaches for removal of unwanted variation in data. Growing use of multiple data sources and development of methods for data integration increases the demand on data preprocessing and also on the ability to generate data of high quality and reproducibility.The aims of applying preprocessing are discussed together with the recognized benefits and drawbacks this has on data and model quality.
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| 20. |
- Waymond, Rodgers, et al.
(författare)
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Combining experiential and conceptual learning in management and accounting education
- 2016
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Ingår i: Academy of Management. - New York : Academy of Management.
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Konferensbidrag (refereegranskat)abstract
- Within management and accounting education both conceptual and experiential learning have been important learning approaches. However, while experiential learning has been extensively studied in accounting education the critical role of conceptual learning has received considerably less attention. In this article we review theory and research to develop a framework that relates to both conceptual and experiential learning. We use a Throughput Model to suggest and demonstrate that both learning cycles can live alongside each other to support accounting education from both student and educator perspectives. Based on our review and combination we suggest implications for the design and implementation of management and accounting education. Copyright © 2016, Academy of Management
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| 21. |
- Åkesson, Lina, et al.
(författare)
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Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats
- 2011
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 7:4, s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes.
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