Mixture designs for constrained components in orthogonal blocks

It is often the case in mixture experiments that some of the ingredients, such as additives or flavourings, are included with proportions constrained to lie in a restricted interval, while the majority of the mixture is made up of a particular ingredient used as a filler. The experimental region in such cases is restricted to a parallelepiped in or near one corner of the full simplex region. In this paper, orthogonally blocked designs with two experimental blends on each edge of the constrained region are considered for mixture experiments with three and four ingredients. The optimal symmetric orthogonally blocked designs within this class are determined and it is shown that even better designs are obtained for the asymmetric situation, in which some experimental blends are taken at the vertices of the experimental region. Some examples are given to show how these ideas may be extended to identify good designs in three and four blocks. Finally, an example is included to illustrate how to overcome the problems of collinearity that sometimes occur when fitting quadratic models to experimental data from mixture experiments in which some of the ingredient proportions are restricted to small values.     

A-optimal designs for optimum mixture in an additive quadratic mixture model

In the analysis of experiments with mixtures, quadratic models have been widely used. The optimum designs for the estimation of optimum mixing proportions in a quadratic mixture model have been studied by Pal and Mandal [Optimum designs for optimum mixtures. Statist Probab Lett. 2006;76:1369–1379] and Mandal et al. [Optimum mixture designs: a pseudo-Bayesian approach. J Ind Soc Agric Stat. 2008;62(2):174–182; Optimum mixture designs under constraints on mixing components. Statist Appl. 2008;6(1&2) (New Series): 189–205], using a pseudo-Bayesian approach. In this paper, a similar approach has been employed to obtain the A-optimal designs for the estimation of optimum proportions in an additive quadratic mixture model, proposed by Darroch and Waller [Additivity and interaction in three-component experiments with mixture. Biometrika. 1985;72:153–163], when the number of components is 3, 4 and 5. It has been shown that the vertices of the simplex are necessarily the support points of the optimum design, and the other support points include barycentres of depth at most 2.     

Nearly optimal orthogonally blocked desings for a quadratic mixture model with q components

In experiments with mixtures involving process variables, orthogonal block designs may be used to allow estimation of the parameters of the mixture components independently of estimation of the parameters of the process variables. In the class of orthogonally blocked designs based on pairs of suitably chosen Latin squares, the optimal designs consist primarily of binary blends of the mixture components, regardless of how many ingredients are available for the mixture. This paper considers ways of modifying these optimal designs so that some or all of the runs used in the experiment include a minimum proportion of each mixture ingredient. The designs considered are nearly optimal in the sense that the experimental points are chosen to follow ridges of maxima in the optimality criteria. Specific designs are discussed for mixtures involving three and four components and distinctions are identified for different designs with the same optimality properties. The ideas presented for these specific designs are readily extended to mixtures with q>4 components.     

Developing mixture models,are we done

Forty-one years ago, Scheffé’s pioneering article “Experiments With Mixtures”, was the impetus for much of the research on mixture experiments performed during the next three decades and into the 1990’s. That article introduced the simplex lattice designs and the associated canonical polynomials, the latter often referred to as Scheffé’s models. Over the years, alternative designs and models have been developed mainly to deal with such modifications to the standard mixture problem as the placing of additional constraints on the mixture component proportions and the inclusion of nonmixture factors called process variables or the amount of the mixture. As we move into the 21st century and think about future research on models for mixture experiments, we are tempted to ask, “Are there additional challenges facing us or are we done” To answer this question truthfully we must look back to see where we’ve been and look to the future at what it is we want to accomplish. This paper is the beginning of this process.     

Projection designs for mixture experiments in orthogonal blocks

Mixture experiments are often carried out in the presence of process variables, such as days of the week or different machines in a manufacturing process, or different ovens in bread and cake making. In such experiments it is particularly useful to be able to arrange the design in orthogonal blocks, so that the model in tue mixture vanauies may ue iitteu inucpenuentiy or tne UIOCK enects mtrouuceu to take account of the changes in the process variables. It is possible in some situations that some of the ingredients in the mixture, such as additives or flavourings, are present in soian quantities, pernaps as iuw a.s 5% ur even !%, resulting in the design space being restricted to only part of the mixture simplex. Hau and Box (1990) discussed the construction of experimental designs for situations where constraints are placed on the design variables. They considered projecting standard response surface designs, including factorial designs and central composite designs, into the restricted design space, and showed that the desirable property of block orthogonality is preserved by the projections considered. Here we present a number of examples of projection designs and illustrate their use when some of the ingredients are restricted to small values, such that the design space is restricted to a sub-region within the usual simplex in the mixture variables.     

Optimum mixture designs in a restricted region

In a mixture experiment, the response depends on the proportions of the mixing components. Canonical models of different degrees and also other models have been suggested to represent the mean response. Optimum designs for estimation of the parameters of the models have been investigated by different authors. In most cases, the optimum design includes the vertex points of the simplex as support points of the design, which are not mixture combinations in the true non-trivial sense. In this paper, optimum designs have been obtained when the experimental region is an ellipsoidal subspace of the entire factor space which does not cover the vertex points of the simplex.     

MODELS AND DESIGNS FOR EXPERIMENTS WITH MIXTURES

Properties such as the tensile strength of an alloy of. different metals and the freezing point of a mixture of liquid chemicals, depend on the proportions (by weight or volume) of the components present and not on the total amount of the mixture. In choosing a model to relate such a property to the proportions of the various components of the mixture, there arise intriguing difficulties due to the fact that proportions sum to unity. It is demonstrated how to construct models which allow for the possibility of inactive components (components that do not affect the property at all) or components with additive effects. The design of experiments to fit such models to data is then discussed with a view to determining whether a given component is inactive or has an additive effect. The optimal allocation of observations to simplex-lattice designs is considered for one of these models. The construction of D -optimal designs for these models is an open problem.     

Symmetry in mixture experiments

Two types of symmetry can arise when the proportions of mixture components are constrained by upper and lower bounds. These two types of symmetry are shown to be useful for blocking first-order designs, as well as for finding the centroid of the experimental region. Orthogonal blocking of first-order mixture designs provides a method of including process variables in the mixture experiment, with the mixture terms orthogonal to the process factors. Symmetric regions are used to develop spherical and rotatable response surface designs for mixtures. The central composite design and designs based on the icosahedron and the dodecahedron are given for four-component mixtures. The uniform shell designs are three-level designs when applied to mixture experiments.     

A Likelihood-Based Approximation to the Cumulative Distribution Function of the Noncentral t Distribution

Optimal designs for estimating the parameters and also the optimum factor combinations in multiresponse experiments have been considered by various authors. However, till date, in mixture experiments optimum designs have been studied only in the single response case. In this article, attempt has been made to investigate optimum designs for estimating optimum mixing proportions in a multiresponse mixture experiment.     

Optimal orthogonal block designs for a quadratic mixture model for three components

In experiments with mixtures that involve process variables, if the response function is expressed as the sum of a function of mixture components and a function of process variables, then the parameters in the mixture part and in the process part can be estimated independently using orthogonal block designs. This paper is concerned with such a block design for parameter estimation in the mixture part of a quadratic mixture model for three mixture components. The behaviour of the eigenvalues of the moment matrix of the design is investigated in detail, the design is optimized according to E- and Aoptimality criteria, and the results are compared together with a known result on Doptimality. It is found that this block design is robust with respect to these diff erent optimality criteria against the shifting of experimental points. As a result, we recommend experimental points of the form (a, b, c) in the simplex S2, where c=0, b=1-a, and a can be any value in the range 0.17+/-0.02.     

Restricted region designs for multifactor mixture experiments

Designs for multifactor mixture experiments in which the component proportions are restricted by some specified lower and upper limits, are called restricted region designs (RRD) for multifactor mixture experiments. In this paper (i) a method of construction of designs for multifactor mixture experiments and (ii) two methods of constructing RRD for multifactor mixture experiments are described. Examples to illustrate the methods of construction have been given.     

DUAL‐OBJECTIVE OPTIMAL MIXTURE DESIGNS

Mixture experiments are widely used in many industries and particularly in the manufacture of consumer products. Almost all work to date assumes a single study objective, which is unrealistic. Researchers may want to estimate model parameters and make predictions or extrapolations at the same time. We discuss design issues for determining the optimal proportions of the mixture components when there are two or more objectives in the study and there is a large sample size. We present a general methodology for constructing two types of dual‐objective optimal design for mixture experiments and discuss the general applicability of the design strategy to more complicated types of mixture design problems, including mixture experiments.     

A new model and class of designs for mixture experiments with process variables

Experiments that involve the blending of several components are known as mixture experiments. In some mixture experiments, the response depends not only on the proportion of the mixture components, but also on the processing conditions, A new combined model is proposed which is based on Taylor series approximation and is intended to be a compromise between standard mixture models and standard response surface models. Cost and/or time constraints often limit the size of industrial experiments. With this in mind, we present a new class of designs that will accommodate the fitting of the new combined model.     

Design and analysis of mixture experiments with process variable

A mixture experiment is an experiment in which the response is assumed to depend on the relative proportions of the ingredients present in the mixture and not on the total amount of the mixture. In such experiment process, variables do not form any portion of the mixture but the levels changed could affect the blending properties of the ingredients. Sometimes, the mixture experiments are costly and the experiments are to be conducted in less number of runs. Here, a general method for construction of efficient mixture experiments in a minimum number of runs by the method for projection of efficient response surface design onto the constrained region is obtained. The efficient designs with a less number of runs have been constructed for 3rd, 4th, and 5th component of mixture experiments with one process variable.     

Mixture and mixture–process variable experiments for pharmaceutical applications

Many experiments in research and development in the pharmaceutical industry involve mixture components. These are experiments in which the experimental factors are the ingredients of a mixture and the response variable is a function of the relative proportion of each ingredient, not its absolute amount. Thus the mixture ingredients cannot be varied independently. A common variation of the mixture experiment occurs when there are also one or more process factors that can be varied independently of each other and of the mixture components, leading to a mixture–process variable experiment. We discuss the design and analysis of these types of experiments, using tablet formulation as an example. Our objective is to encourage greater utilization of these techniques in pharmaceutical research and development. Copyright © 2004 John Wiley & Sons Ltd.     

Mixture experiments with mixing errors

In mixture experiments the properties of mixtures are usually studied by mixing the amounts of the mixture components that are required to obtain the necessary proportions. This paper considers the impact of inaccuracies in discharging the required amounts of the mixture components on the statistical analysis of the data. It shows how the regression calibration approach can be used to minimize the resulting bias in the model and in the estimates of the model parameters, as well as to find correct estimates of the corresponding variances. Its application is made difficult by the complex structure of these errors. We also show how knowledge of the form of the model bias allows for choosing a manufacturing setting for a mixture product that is not biased and has smaller signal to noise ratio.     

D-Optimum Designs for Optimum Mixture in a Quadratic Log Contrast Model

Optimal designs for estimating the optimum mixing proportions in a quadratic mixture model was first investigated by Pal and Mandal (2006). In this article, similar investigation is carried out when mean response in a mixture experiment is described by a quadratic log contrast model. It is found that in a symmetric subspace of the finite dimensional simplex, there exists a D-optimal design that puts weights at the centroid of the sub-space and the vertices of the experimental domain. The optimality is checked by numerical computation using Equivalence Theorem.     

Optimum Designs for Estimation of Parameters in a Quadratic Mixture-Amount Model

The authors propose a mixture-amount model, which is quadratic both in the proportions of mixing components and the amount of mixture. They attempt to find the A- and D-optimal designs for the estimation of the model parameters within a subclass of designs. The optimality of the derived designs in the entire class of competing designs has been investigated through equivalence theorem.     

A- and D-optimal designs for a log contrast model for experiments with mixtures

A- and D-optimal designs are investigated for a log contrast model suggested by Aitchison & Bacon-Shone for experiments with mixtures. It is proved that when the number of mixture components q is an even integer, A- and D-optimal designs are identical; and when q is an odd integer, A- and D-optimal designs are different, but they share some common support points and are very close to each other in efficiency. Optimal designs with a minimum number of support points are also constructed for 3, 4, 5 and 6 mixture components.     

A graphical method for evaluating mixture designs with respect to the slope

Good estimation of the slopes of the mixture response function may be important as well as estimation of mean mixture response. It is possible to evaluate and compare several mixture designs with respect to the slope. A graphical method is proposed that allows us to evaluate a given design's support for the fitted model in terms of slope variance. We can plot variances of slopes along Cox direction or axial direction according to existence of restriction of simplex region or not when comparing several different mixture designs.